This research was supported by the National Research Foundation of Korea (NRF-2020R1A2C1007102 and 2021R1A5A6002803) with the Center for New Directions in Organic Synthesis and an HUFS Grant 2022.

1. Synthesis of the diastereomeric mixture of chiral aziridine (-)-mentholyl ester derivative (1)
<ol>
	<li>Add 2,3-dibromopropane (-)-menthol ester 1a (5.0 g, 13.58 mM, 1.0 equiv) and a magnetic stirring bar into an oven-dried 250 mL two-neck round-bottom flask under nitrogen (N2) atmosphere.</li>
	<li>Add anhydrous acetonitrile (60 mL) to the reaction flask using an airtight syringe.</li>
	<li>Then cool the reaction mixture at 0 &#176;C using an ice bath and stir the reaction mixture for 5 min.</li>
	<li>Add potassium carbonate (5.6 g, 40.74 mM, 3.0 equiv) into the reaction mixture at the same temperature and allow to stir for 30 min.</li>
	<li>Add (2R)-phenylethylamine (2.0 mL, 16.29 nM, 1.2 equiv) in a dropwise manner at room temperature (RT) and allow the reaction mixture to stir for 12 h.</li>
	<li>Monitor the progress of reaction using thin layer chromatography by using 9:1 v/v hexane:ethyl acetate (EtOAc; Rf = 0.4) as an eluent.</li>
	<li>After the reaction is complete, filter the mixture over filter paper (pore size 70 mm).</li>
	<li>Then, add water (30 mL) into the organic filtrate and extract the organic layer with Et2O (2 x 50 mL) two times using a separating funnel.</li>
	<li>Dry the combined organic extracts over 7.5 g of anhydrous Na2SO4 and concentrate in vacuo (&#60;15 mbar) using a rotary evaporator. 
	NOTE: Now a crude mixture of diastereomeric chiral aziridine containing both isomers of (R)-(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl1-((R)-1-phenylethyl)aziridine-2-carboxylate and (S)-(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl1-((R)-1-phenylethyl)aziridine-2-carboxylate (4.1 g, 90%) is obtained.</li>
	<li>Isolation of chiral aziridine (R)-(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl 1-((R)-1- phenylethyl)aziridine-2-carboxylate (2) by a selective crystallization method
	<ol>
		<li>Add 8.7 g of the crude mixture of chiral aziridine (-)-Menthol ester 1 derivative and dissolve in 70 mL of methanol to an oven-dried 250 mL single-neck round-bottom flask.</li>
		<li>Now warm the reaction mixture up to 70 &#176;C by using a hot water bath, then cool the reaction mixture at -10 &#176;C until solid crystal forms.</li>
		<li>Filter the solid compound over a filter paper (pore size 70 mm) to obtain 2.2 g of (R)-(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl 1-((R)-1-phenylethyl)aziridine-2-carboxylate (2) ester.</li>
		<li>Concentrate the filtrate solution again in vacuo (&#60;15 mbar) using a rotary evaporator, dissolve 50 mL of ethanol in the remaining reaction mixture and recrystallize at -10 &#176;C to obtain 1.2 g of (R)-(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl 1-((R)-1-phenylethyl)aziridine-2-carboxylate (2).</li>
		<li>At this time, use the other alcohol ethanol in the same way as methanol.</li>
		<li>After recrystallization, again filter over a filter paper (pore size 70 mm), concentrate the remaining crude 5.3 g of filtrate solution completely in vacuo (&#60;15 mbar) using a rotary evaporator, and add 50 mL of a pentane hydrocarbon solvent.</li>
		<li>Keep the remaining reaction solution at -15 &#176;C. 
		NOTE: Now a solid compound of nearly 1.9 g of (S)-(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl1-((R)-1-phenylethyl)aziridine-2-carboxylate ester (3) is obtained.</li>
		<li>After obtaining crystals, concentrate the solution again in vacuo (&#60;15 mbar) using a rotary evaporator and dissolve it in 30 mL of pentane hydrocarbon solvent.</li>
		<li>Recrystallize again at -15 &#176;C to obtain 0.8 g of (S)-(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl1-((R)-1-phenylethyl)aziridine-2-carboxylate ester (2&#39;).</li>
	</ol>
	</li>
	<li>Obtaining (R)-ethyl 1-((R)-1-phenylethyl)aziridine-2-carboxylate (3)
	<ol>
		<li>Add (R)-(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl1-((R)-1-phenylethyl)aziridine-2-carboxylate (2) (0.167 g, 0.57 mM) and a magnetic stir-bar into an oven-dried 25 mL two-neck round-bottom flask under nitrogen (N2) atmosphere.</li>
		<li>Add 1.8 mL of ethanol to the reaction flask using an airtight syringe and stir it at RT.</li>
		<li>Then add potassium carbonate (0.40 g, 20.28 mmol, 4.0 equiv) and stir it at RT for 2 days.</li>
		<li>Monitor the progress of reaction using thin layer chromatography (eluent, 8:2 v/v, hexane:ethyl acetate (EtOAc), Rf = 0.6).</li>
		<li>After the reaction is completed, filter the mixture over filter paper (pore size 70 mm), then add water (5 mL) into the organic filtrate and extract the organic layer with CH2Cl2 (2 x 15 mL) two times by using a separating funnel.</li>
		<li>Dry the combined organic extracts over 3.0 g of anhydrous Na2SO4 and concentrate in vacuo (&#60;15 mbar) using a rotary evaporator.</li>
		<li>Purify the crude product by normal phase column chromatography on silica gel (70-230 mesh) to afford a pure product (R)-ethyl 1-((R)-1-phenylethyl)aziridine-2-carboxylate (3) (950 mg, 88%). Rf (30% EtOAc/hexane = 0.50).</li>
	</ol>
	</li>
</ol>
2. Regio and stereoselective aziridine ring-opening by azide nucleophile for the total synthesis of biemamide B and biemamide D
<ol>
	<li>Synthesis of (R)-ethyl 2-azido-3-(((R)-1-phenylethyl)amino)propanoate (5)
	<ol>
		<li>Transfer (500 mg, 2.20 mM, 1.0 equiv) of chiral (S)-ethyl 1-((R)-1-phenylethyl)aziridine-2-carboxylate (4) and a magnetic stir-bar into an oven-dried 50 mL two-neck round-bottom flask under open atmosphere.</li>
		<li>Add 50% aqueous ethanol (15 mL) to the reaction mixture.</li>
		<li>Cool the reaction mixture at 0 &#176;C and add concentrated sulfuric acid (36 N) dropwise to maintain nearly pH 4.0, and stir for 5 min.</li>
		<li>Add sodium azide (370 mg, 5.70 mM, 2.5 equiv) at 0 &#176;C and allow the reaction mixture to stir for 10 min at the same temperature and then warm at RT.</li>
		<li>Then, add AlCl3&#8729;6H2O (55 mg, 0.22 mM, 0.1 equiv) as a catalyst at the same RT and allow to stir for an additional 3 h.</li>
		<li>Monitor the progress of reaction using thin layer chromatography (eluent, 6:4 v/v, hexane:ethyl acetate (EtOAc), Rf = 0.2).</li>
		<li>Quench the reaction mixture with two portions of 20 mL saturated NaHCO3.</li>
		<li>Then filter the crude mixture over a celite pad with ethanol (2 x 10 mL).</li>
		<li>Concentrate the reaction mixture in vacuo (&#60;15 mbar) using a rotary evaporator.</li>
		<li>Extract the organic layer with CH2Cl2 (2 x 50 mL) two times using a separating funnel.</li>
		<li>Then dry the combined organic layer over 5.0 g of anhydrous Na2SO4 for 5 min.</li>
		<li>Concentrate the&#160;crude organic layer in vacuo (&#60;15 mbar) using a rotary evaporator&#160;to afford a crude azide product.</li>
		<li>Purify the crude product with normal phase column chromatography on silica gel (70-230 mesh) by eluting with 40% EtOAc/hexane (Rf = 0.20) to afford 490 mg (90% yield) of (R)-ethyl 2-azido-3-(((R)-1-phenylethyl)amino)propanoate (5) as a viscous liquid.</li>
	</ol>
	</li>
	<li>Synthesis of (9H-Fluoren-9-yl)methyl(3-(((R)-3-methyl-2,4-dioxo-1-((R)-1 phenylethyl)hexahydro pyrimidin-5-yl)amino)-3-oxopropyl)carbamate (7)
	<ol>
		<li>Transfer 150 mg of chiral (R)-5-amino-3-methyl-1-((R)-1-phenylethyl) dihydropyrimidine-2,4(1H,3H)-dione (6) (150 mg, 0.60 mM, 1.0 equiv) and a magnetic stir-bar into an oven-dried 25 mL two-neck round-bottom flask under N2 atmosphere.</li>
		<li>Add dry CH2Cl2 (15.0 mL) to the reaction flask using an airtight syringe.</li>
		<li>Then cool the reaction mixture at 0 &#176;C using an ice bath and stir the reaction mixture for 5 min.</li>
		<li>Add Fmoc-beta-alanine (377 mg, 1.20 mM, 2.0 equiv) and DIPEA (0.67 mL, 3.64 mM, 6.0 equiv) at 0 &#176;C and stir it for 5 min.</li>
		<li>Add EDCI (347 mg, 1.82 mM, 3.0 equiv) and HOBt (165 mg, 1.21 mM, 2.0 equiv) to the reaction mixture at 0 &#176;C and allow to stir for 10 min at the same temperature.</li>
		<li>Keep the reaction mixture at RT and allow to stir for an additional 8 h.</li>
		<li>Monitor the progress of reaction using thin layer chromatography using (2:8 v/v, hexane:ethyl acetate (EtOAc), Rf = 0.4) as an eluent.</li>
		<li>Quench the reaction mixture with water (10 mL).</li>
		<li>Wash the combined organic layer with brine (15 mL), then extract the organic layer with CH2Cl2 (2 x 20 mL) two times using a separating funnel.</li>
		<li>Then dry the combined organic layer over 5.0 g of anhydrous Na2SO4 for 5 min and concentrate it in vacuo (&#60;15 mbar) using a rotary evaporator.</li>
		<li>Purify the crude product with normal phase column chromatography on silica gel (70-230 mesh) by eluting with 80% EtOAc/hexane (Rf&#160;= 0.40) to afford 295 mg of (7) (90% yield).</li>
	</ol>
	</li>
</ol>
3. Stereoselective Mukaiyama aldol reaction with chiral aziridine-2-carboxaldehyde and Its regio and stereoselective aziridine ring-opening by internal hydroxy nucleophile for the total synthesis of (-)- epiallo-somuscarine (17)
<ol>
	<li>Synthesis of (S)-4-hydroxy-4-((R)-1-((R)-1-phenylethyl)aziridin-2-yl)butan-2-one (12)
	<ol>
		<li>Transfer (R)-1-((R)-1-phenylethyl)aziridine-2-carbaldehyde (10) (140 mg, 0.8 mM, 1.0 equiv) and a magnetic stir-bar into an oven-dried 25 mL two-neck round-bottom flask under N2 atmosphere.</li>
		<li>Add dry CH3CN (4.0 mL) to the reaction flask using an airtight syringe.</li>
		<li>Then cool the reaction mixture at -20 &#176;C using an ice-acetone bath and stir the reaction mixture for 5 min.</li>
		<li>Add ZnCl2 anhydrous (108 mg, 0.8 mM, 1.0 equiv) to the reaction mixture at -20 &#176;C and allow to stir for 5 min.</li>
		<li>Then add trimethyl(prop-1-en-2-yloxy)silane (11) (104 mg, 0.8 mM, 1.0 equiv) dissolved in dry CH3CN (3.0 mL) to the reaction mixture at -20 &#176;C in a dropwise manner and allow the reaction mixture to stir for 1 h at the same temperature.</li>
		<li>Monitor the progress of reaction using thin layer chromatography using 8:2 v/v hexane:ethyl acetate (EtOAc), Rf = 0.2) as an eluent.</li>
		<li>Quench the reaction mixture with saturated NaHCO3 (4 mL).</li>
		<li>Extract the organic layer with EtOAc (2 x 15 mL) two times using a separating funnel.</li>
		<li>Dry the combined organic layer with 3.0 g of anhydrous Na2SO4 and concentrate it in vacuo (&#60;15 mbar) using a rotary evaporator.</li>
		<li>Purify the crude product with normal phase column chromatography on silica gel (70-230 mesh) by eluting with 80% EtOAc/hexane, (Rf = 0.20) to afford 58 mg of (S)-4-hydroxy-4-((R)-1-((R)-1-phenylethyl)aziridin-2-yl)butan-2-one) (12) (85% yield).</li>
	</ol>
	</li>
	<li>Synthesis of (R)-N-(((2R,3S,5R)-3-((tert-butyldimethylsilyl)oxy)-5-methyltetra hydrofuran-2-yl)methyl)-1-phenylethanamine (15)
	<ol>
		<li>Transfer (S)-4-((tert-butyldimethylsilyl)oxy)-4-((R)-1-((R)-1-phenylethyl) aziridin-2-yl)butan-2-one (13) (400 mg, 1.15 mM, 1.0 equiv) and a magnetic stir-bar into an oven-dried 25 mL two-neck round-bottom flask under N2 atmosphere.</li>
		<li>Add anhydrous THF (50 mL) to the reaction flask using an airtight syringe.</li>
		<li>Cool the reaction mixture at -78 &#176;C using a dry ice-acetone bath and allow to stir for 5 min.</li>
		<li>Then add lithium tri-sec-butylborohydride (L-selectride) (1 M solution in THF) (2.3 mL, 2.0 equiv) dropwise into the reaction mixture at -78 &#176;C and allow to stir for another 25 min.</li>
		<li>Warm the reaction mixture to RT and allow to stir for 8 h.</li>
		<li>Monitor the progress of the reaction by TLC using 30% EtOAc/hexane (Rf = 0.40) as an eluent.</li>
		<li>After the complete consumption of compound 13, quench the reaction mixture with 0.1 M of NaOH (5 mL).</li>
		<li>Extract the organic layer with EtOAc (3 x 15 mL), then wash with brine (15 mL).</li>
		<li>Dry the organic layer over 3.0 g of anhydrous Na2SO4 and concentrate in vacuo (&#60;15 mbar) using a rotary evaporator.</li>
		<li>Purify the crude product with normal phase column chromatography on silica gel (70-230 mesh, eluent, 8:2 v/v, hexane:ethyl acetate (EtOAc), Rf = 0.2) to afford a pure compound (15) (382 mg, 95% yield).</li>
	</ol>
	</li>
	<li>Synthesis of (-)-epiallo-isomuscarine iodide (17)
	<ol>
		<li>Transfer compound 16 (20 mg, 0.15 mM, 1.0 equiv) and a magnetic stir bar into an oven-dried 10 mL round-bottom flask under N2 atmosphere.</li>
		<li>Add 3 mL of EtOAc reaction flask using an airtight syringe.</li>
		<li>Then add Methyl iodide (0.4 mL, 3.0 mM) to the reaction mixture at RT.</li>
		<li>Add 1,2,2,6,6-pentamethylpiperidine (PMP) (0.05 mL, 0.3 mM, 2.0 equiv) to the reaction mixture at 0 &#176;C.</li>
		<li>Then, keep the reaction mixture at RT and allow to stir for an additional 16 h.</li>
		<li>Evaporate the solvent in vacuo (&#60;15 mbar) using a rotary evaporator to give the crude product.</li>
		<li>Wash three times by adding (3 x 5 mL) 10% MeOH in EtOAc to the crude reaction mixture.</li>
		<li>Then wash the crude mixture with n-Pentane (5 mL) and concentrate under vacuum (&#60;15 mbar) using a rotary evaporator to achieve pure (-)-epiallo-isomuscarine iodide (17) (32 mg, 68%).</li>
	</ol>
	</li>
</ol>
4. Characterization of all products
<ol>
	<li>Characterize all the new compounds by 1H, 13C NMR spectroscopy, and high-resolution mass spectrometry (HRMS)7,8,11.</li>
</ol>

<ol>
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The authors declare that there was no conflict of interest in this study.

Aziridines as nitrogen-containing three-membered heterocycles have enormous potential for synthetic starting martials or intermediates to prepare nitrogen-rich organic molecules. Based on the group bearing at the ring nitrogen, they are classified as "activated" and "non-activated" aziridines whose chemical reactivity and selectivity are different. However, very limited methods are available to prepare this valuable aziridine in an optically active form. 
The protocol in this paper describes a...

Small rings consisting of cyclopropanes, oxiranes, and aziridines are found in various compounds such as natural products and drugs1,2.&#160;They are primarily used as starting materials exploiting their ring strain. Among the three-ring compounds, aziridine has been studied less extensively due to its instability and uncontrollable reactivity3. As shown in the electrostatic potential maps (Figure 1), a group attached to the aziridine ring-nitrogen, whether electron-donating or electron-attracting, makes the basicity of nitrogen different. This difference provides a striking contrast to the reactivity and selectivity of the corresponding aziridines.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/63705/63705fig01.jpg" /> 
Figure 1: Chemical structures of &#34;activated&#34; and &#34;non-activated&#34; aziridines and electrostatic potential maps of their representative examples N-methylaziridine, and N-acetylaziridine4. This figure has been modified with permission from Ranjith et al.4. <a href="https://jove.unicartagenaproxy.elogim.com/files/ftp_upload/63705/63705fig01large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
When the ring nitrogen has an electron-withdrawing group, such as sulfonate, phosphonate, and carbamate, we call it &#34;activated&#34; aziridine. This is readily reactive with nucleophiles to compensate for its instability with a limited scope of regiochemistry. These activated aziridines are prepared through various catalytic methods and used as a starting material. Much of recent aziridine chemistry has dealt with these activated aziridines. However, activated aziridines suffer certain restrictions resulting from their instability and limited reaction scope of the ring opening. On the other hand, aziridines bearing electron-donating substituents, like alkyl or substituted alkyl groups, at the ring nitrogen called &#34;non-activated&#34;4, are relatively stable under most circumstances and can be left on the bench for a long time without significant decomposition. The nucleophilic ring-opening reactions of non-activated aziridine occur via the formation of aziridinium ions. Most reactions of aziridine ring-opening and ring transformations proceed in a highly regiochemical manner. However, very few literature reports discuss the preparation of optically pure non-activated aziridines with substituents at the C2 or C3 positions5,6.
This paper shows the successful preparation of &#945;-methylbenzyl group-containing chiral aziridine-2-carboxylate derivatives, specifically (-)-mentholyl (1R)-phenylethylaziridine-2-carboxylates as its diastereomeric mixture, from the reaction of 2,3-dibromopropionate and (1R)-phenylethylamine. From this diastereomeric mixture, enantiopure (1R)-phenylethyl-(2R)- and (2S)-aziridine-2-carboxylates as their (-)-mentholyl esters were obtained in optically pure forms by selective recrystallization from MeOH and n-pentane on multi-hundred-kilo scales (Figure 1)7. These (-)-mentholyl esters can be easily converted into their ethyl or methyl esters by transesterification in the presence of magnesium or potassium carbonate7. These compounds can also be prepared easily on a laboratory scale from the reactions of alkyl 2,3-dibromopropionates or the vinyl triflate of &#945;-ketoester with chiral 2-phenylethylamine followed by separation of the diastereomeric mixture using simple flash column chromatography8.
Once we have enantiopure chiral aziridine-2-carboxylate, we can synthesize various cyclic and acyclic nitrogen-containing biologically important target molecules based on functional group transformations of carboxylate and highly regio- and stereoselective aziridine-ring opening reactions6,9,10. The first expedient asymmetric synthesis was applied for both enantiomers of 5, 6-dihydrouracil-type marine natural products biemamide B and D as potential TGF-&#946; inhibitors11,12. Secondly, the diastereoselective synthesis of &#946;-(aziridin-2-yl)-&#946;-hydroxy ketones was achieved by Mukaiyama aldol reaction of optically pure 1-(1-phenylethyl)-aziridine-2-carboxaldehyde and various enol silanes in the presence of ZnCl2, in high yield (&#62;82%) with almost perfect stereoselectivity (98:2 dr) via a chelation-controlled transition state. These were used for the asymmetric synthesis of epiallo-isomuscarine alkaloids13,14,15.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>(2R)-1-[(1R)-1-Phenylethyl]-2-aziridinecarboxylic acid (-)-menthol ester, 98%</td>
			<td>Sigma-Aldrich</td>
			<td>57054-0</td>
			<td></td>
		</tr>
		<tr>
			<td>(2S)-1-[(1R)-1-Phenylethyl]-2-aziridinecarboxylic acid (-)-menthol ester</td>
			<td>Sigma-Aldrich</td>
			<td>57051-6</td>
			<td></td>
		</tr>
		<tr>
			<td>1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride</td>
			<td>TCI</td>
			<td>424331-25 g</td>
			<td>CAS No: 25952-53-8</td>
		</tr>
		<tr>
			<td>1,4-Dioxane</td>
			<td>SAMCHUN</td>
			<td>D0654-1 kg</td>
			<td>CAS No: 123-91-1</td>
		</tr>
		<tr>
			<td>1-Hydroxybenzotriazole hydrate</td>
			<td>Aldrich</td>
			<td>219-989-7-50 g</td>
			<td>CAS No: 123333-53-9</td>
		</tr>
		<tr>
			<td>2,6-Lutidine</td>
			<td>Alfa Aesar</td>
			<td>A10478-AP, 500 mL</td>
			<td>CAS No: 108-48-5</td>
		</tr>
		<tr>
			<td>Acetonitrile</td>
			<td>SAMCHUN</td>
			<td>A0127-18&#160; L</td>
			<td>CAS No: 75-05-8</td>
		</tr>
		<tr>
			<td>Acetonitrile-d3</td>
			<td>Cambridge Isotope Laboratories,</td>
			<td>15G-744-25 g</td>
			<td>CAS No: 2206-26-0</td>
		</tr>
		<tr>
			<td>Aluminum chloride hexahydrate</td>
			<td>Aldrich</td>
			<td>231-208-1, 500 g</td>
			<td>CAS No : 7784-13-6</td>
		</tr>
		<tr>
			<td>Bruker AVANCE III HD (400 MHz) spectrometer</td>
			<td>Bruker</td>
			<td>NA</td>
			<td></td>
		</tr>
		<tr>
			<td>Chloroform-d</td>
			<td>Cambridge Isotope Laboratories,</td>
			<td>&#160;100 g</td>
			<td>CAS No: 865-49-6</td>
		</tr>
		<tr>
			<td>Dichloromethane</td>
			<td>SAMCHUN</td>
			<td>M0822-18 L</td>
			<td>CAS No: 75-09-2</td>
		</tr>
		<tr>
			<td>Dimethyl sulfoxide-d6</td>
			<td>Cambridge Isotope Laboratories,</td>
			<td>25 g</td>
			<td>CAS No: 2206-27-1</td>
		</tr>
		<tr>
			<td>Ethanol</td>
			<td>EMSURE</td>
			<td>&#160;1009831000,1L</td>
			<td>CAS No: 64-17-5</td>
		</tr>
		<tr>
			<td>Ethyl acetate</td>
			<td>SAMCHUN</td>
			<td>E0191-18 L</td>
			<td>CAS No: 141-78-6</td>
		</tr>
		<tr>
			<td>High resolution mass spectra/MALDI-TOF/TOF Mass Spectrometry</td>
			<td>AB SCIEX</td>
			<td>4800 Plus</td>
			<td>High resolution mass spectra</td>
		</tr>
		<tr>
			<td>JASCO P-2000</td>
			<td>JASCO</td>
			<td>P-2000</td>
			<td>For optical rotation</td>
		</tr>
		<tr>
			<td>Lithium aluminum hydride</td>
			<td>TCI</td>
			<td>L0203-100 g</td>
			<td>CAS No: 16853-85-3</td>
		</tr>
		<tr>
			<td>L-Selectride, 1 M solution in THF</td>
			<td>Acros</td>
			<td>176451000, 100 mL</td>
			<td>CAS No: 38721-52-7</td>
		</tr>
		<tr>
			<td>Methanol</td>
			<td>SAMCHUN</td>
			<td>M0585-18 L</td>
			<td>CAS No: 67-56-1</td>
		</tr>
		<tr>
			<td>N-[(9H-Fluoren-9-ylmethoxy)carbonyl]-&#946;-alanine</td>
			<td>TCI</td>
			<td>F08825G-5 g</td>
			<td>CAS No: 35737-10-1</td>
		</tr>
		<tr>
			<td>N-Ethyldiisopropylamine</td>
			<td>Aldrich</td>
			<td>230-392-0, 100 mL</td>
			<td>CAS No: 7087-68-5</td>
		</tr>
		<tr>
			<td>n-Hexane</td>
			<td>SAMCHUN</td>
			<td>H0114-18 L</td>
			<td>CAS No: 110-54-3</td>
		</tr>
		<tr>
			<td>Ninhydrin</td>
			<td>Alfa Aesar</td>
			<td>A10409-250 g</td>
			<td>CAS No: 485-47-2</td>
		</tr>
		<tr>
			<td>p-Anisaldehyde</td>
			<td>aldrich</td>
			<td>A88107-5 g</td>
			<td>CAS No: 123-11-5</td>
		</tr>
		<tr>
			<td>Phosphomolybdic acid hydrate</td>
			<td>TCI</td>
			<td>P1910-100 g</td>
			<td>CAS No: 51429-74-4</td>
		</tr>
		<tr>
			<td>Sodium azide</td>
			<td>D.S.P</td>
			<td>703301-500 g</td>
			<td>CAS No: 26628-22-8</td>
		</tr>
		<tr>
			<td>Sodium Hydride 60% dispersion in mineral oil</td>
			<td>Sigma-Aldrich</td>
			<td>452912-100 G</td>
			<td>CAS No: 7646-69-7</td>
		</tr>
		<tr>
			<td>Sodium hydroxide</td>
			<td>DUKSAN</td>
			<td>A31226-1 kg</td>
			<td>CAS No: 1310-73-2</td>
		</tr>
		<tr>
			<td>Sodium sulfate</td>
			<td>SAMCHUN</td>
			<td>S1011-1 kg</td>
			<td>CAS No: 7757-82-6</td>
		</tr>
		<tr>
			<td>Thin Layer Chromatography (TLC)</td>
			<td>Merck</td>
			<td>100390</td>
			<td></td>
		</tr>
		<tr>
			<td>Tert-Butyldimethylsilyl trifluoromethanesulfonate, 98%</td>
			<td>Aldrich</td>
			<td>274-102-0, 25 g</td>
			<td>CAS NO: 69739-34-0</td>
		</tr>
		<tr>
			<td>Tetrahydrofuran</td>
			<td>SAMCHUN</td>
			<td>T0148-18 L</td>
			<td>CAS No: 109-99-9</td>
		</tr>
		<tr>
			<td>Triethylethylamine</td>
			<td>DAEJUNG</td>
			<td>8556-4400-1 L</td>
			<td>CAS No: 121-44-8</td>
		</tr>
		<tr>
			<td>UV light</td>
			<td>Korea Ace Sci</td>
			<td>TN-4C</td>
			<td>254 nm</td>
		</tr>
		<tr>
			<td>Zinc chloride, anhydrous, 98+%</td>
			<td>Alfa Aesar</td>
			<td>A16281-22100 g</td>
			<td>CAS No : 7646-85-7</td>
		</tr>
	</tbody>
</table>

preparation of enantiopure non-activated aziridines and synthesis of biemamide b, d, and epiallo-isomuscarine

Nitrogen-containing heterocycle aziridines are synthetically very valuable for the preparation of azacyclic and acyclic molecules. However, it is very difficult and laborious to make aziridines in optically pure forms on a large scale to apply asymmetric synthesis of aza compounds. Fortunately, we successfully achieved both enantiomers (2R)- and (2S)-aziridine-2-carboxylates with the electron-donating &#945;-methylbenzyl group at the ring nitrogen as non-activated aziridines. These starting aziridines have two distinct functional groups-highly reactive three-membered ring and versatile carboxylate. They are applicable in ring-opening or ring-transformation with aziridine and in functional group transformation to others from carboxylate. Both of these enantiomers were utilized in the preparation of biologically important amino acyclic and/or aza-heterocyclic compounds in an asymmetric manner. Specifically, this report describes the first expedient asymmetric synthesis of both enantiomers of 5, 6-dihydrouracil-type marine natural products biemamide B and D as potential TGF-&#946; inhibitors. This synthesis consisted of regio- and the stereoselective ring-opening reaction of aziridine-2-carboxylate and subsequent formation of 4-aminoteterahydropyrimidine-2,4-dione. One more example in this protocol dealt a highly stereoselective Mukaiyama reaction of aziridine-2-carboxylate and silyl enol ether, following intramolecular aziridine ring-opening to provide easy and facile access to (-)-epiallo-isomuscarine.

Here, we report the synthesis of enantiopure aziridine-2-carboxylates. The diastereomeric mixture of (R)-(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl1-((R)-1-phenylethyl)aziridine-2-carboxylate (2) and (S)-(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl1-((R)-1-phenylethyl)aziridine-2-carboxylate (3) (4.1 g, 90%) were prepared in quantitative yield from 2,3 -dibromopropane (-)-mentholyl ester and (1R</em...

Watch this Scientific Journal Video about Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine at JoVE.com

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine

In this study, we prepare both enantiomers of aziridine-2-carboxylate, which are used in the asymmetric synthesis of alkaloids, including biemamide B and D, and (-)-epiallo-isomuscarine.

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine

Nitrogen-containing heterocycle aziridines are synthetically very valuable for the preparation of azacyclic and acyclic molecules. However, it is very ...

preparation-enantiopure-non-activated-aziridines-synthesis-biemamide

Universidad de Cartagena UDEC

Research

JoVE Journal

Chemistry

2.8K Views.  Hankuk University of Foreign Studies. In this study, we prepare both enantiomers of aziridine-2-carboxylate, which are used in the asymmetric synthesis of alkaloids, including biemamide B and D, and (-)-epiallo-isomuscarine.

Video: Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine

Template Directed Synthesis of Plasmonic Gold Nanotubes with Tunable IR Absorbance

A nearly parallel array of pores can be produced by anodizing aluminum foils in acidic environments1, 2. Applications of anodic aluminum oxide (AAO) membranes have been under development since the 1990's and have become a common method to template the synthesis of high aspect ratio nanostructures, mostly by electrochemical growth or pore-wetting. Recently, these membranes have become commercially available in a wide range of pore sizes and densities, leading to an extensive library of functional nanostructures being synthesized from AAO membranes. These include composite nanorods, nanowires and nanotubes made of metals, inorganic materials or polymers 3-10. Nanoporous membranes have been used to synthesize nanoparticle and nanotube arrays that perform well as refractive index sensors, plasmonic biosensors, or surface enhanced Raman spectroscopy (SERS) substrates 11-16, as well as a wide range of other fields such as photo-thermal heating 17, permselective transport 18, 19, catalysis 20, microfluidics 21, and electrochemical sensing 22, 23. Here, we report a novel procedure to prepare gold nanotubes in AAO membranes. Hollow nanostructures have potential application in plasmonic and SERS sensing, and we anticipate these gold nanotubes will allow for high sensitivity and strong plasmon signals, arising from decreased material dampening 15.

Solution-suspendable gold nanotubes with controlled dimensions can be synthesized by electrochemical deposition in porous anodic aluminum oxide (AAO) membranes using a hydrophobic polymer core. Gold nanotubes and nanotube arrays hold promise for applications in plasmonic biosensing, surface-enhanced Raman spectroscopy, photo-thermal heating, ionic and molecular transport, microfluidics, catalysis and electrochemical sensing.

A nearly parallel array of pores can be produced by anodizing aluminum foils in acidic environments1, 2. Applications of anodic aluminum oxide (AAO) ...

Preparation of Silica Nanoparticles Through Microwave-assisted Acid-catalysis

Microwave-assisted synthetic techniques were used to quickly and reproducibly produce silica nanoparticle sols using an acid catalyst with nanoparticle diameters ranging from 30-250 nm by varying the reaction conditions. Through the selection of a microwave compatible solvent, silicic acid precursor, catalyst, and microwave irradiation time, these microwave-assisted methods were capable of overcoming the previously reported shortcomings associated with synthesis of silica nanoparticles using microwave reactors. The siloxane precursor was hydrolyzed using the acid catalyst, HCl. Acetone, a low-tan &#948; solvent, mediates the condensation reactions and has minimal interaction with the electromagnetic field. Condensation reactions begin when the silicic acid precursor couples with the microwave radiation, leading to silica nanoparticle sol formation. The silica nanoparticles were characterized by dynamic light scattering data and scanning electron microscopy, which show the materials&#39; morphology and size to be dependent on the reaction conditions. Microwave-assisted reactions produce silica nanoparticles with roughened textured surfaces that are atypical for silica sols produced by St&#246;ber&#39;s methods, which have smooth surfaces.

Silica nanoparticles were prepared using acid-catalysis of a siloxane precursor and microwave-assisted synthetic techniques resulting in the controlled growth of nanomaterials ranging from 30-250 nm in diameter. The growth dynamics can be controlled by varying the initial silicic acid concentration, time of the reaction, and temperature of reaction.

Microwave-assisted synthetic techniques were used to quickly and reproducibly produce silica nanoparticle sols using an acid catalyst with nanoparticle ...

Preparation of Hydrophobic Metal-Organic Frameworks via Plasma Enhanced Chemical Vapor Deposition of Perfluoroalkanes for the Removal of Ammonia

Plasma enhanced chemical vapor deposition (PECVD) of perfluoroalkanes has long been studied for tuning the wetting properties of surfaces. For high surface area microporous materials, such as metal-organic frameworks (MOFs), unique challenges present themselves for PECVD treatments. Herein the protocol for development of a MOF that was previously unstable to humid conditions is presented. The protocol describes the synthesis of Cu-BTC (also known as HKUST-1), the treatment of Cu-BTC with PECVD of perfluoroalkanes, the aging of materials under humid conditions, and the subsequent ammonia microbreakthrough experiments on milligram quantities of microporous materials. Cu-BTC has an extremely high surface area (~1,800 m2/g) when compared to most materials or surfaces that have been previously treated by PECVD methods. Parameters such as chamber pressure and treatment time are extremely important to ensure the perfluoroalkane plasma penetrates to and reacts with the inner MOF surfaces. Furthermore, the protocol for ammonia microbreakthrough experiments set forth here can be utilized for a variety of test gases and microporous materials.

Herein the procedures for plasma enhanced chemical vapor deposition of perfluoroalkanes on microporous materials such as metal-organic frameworks to enhance their stability and hydrophobicity are described. Furthermore, breakthrough testing of milligram quantities of samples is described in detail.

Plasma enhanced chemical vapor deposition (PECVD) of perfluoroalkanes has long been studied for tuning the wetting properties of surfaces. For high ...

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents

Amide coupling reactions can be used to synthesize bispyridine-based ligands for use as bridging linkers in multinuclear platinum anticancer drugs. Isonicotinic acid, or its derivatives, are coupled to variable length diaminoalkane chains under an inert atmosphere in anhydrous DMF or DMSO with the use of a weak base, triethylamine, and a coupling agent, 1-propylphosphonic anhydride. The products precipitate from solution upon formation or can be precipitated by the addition of water. If desired, the ligands can be further purified by recrystallization from hot water. Dinuclear platinum complex synthesis using the bispyridine ligands is done in hot water using transplatin. The most informative of the chemical characterization techniques to determine the structure and gross purity of both the bispyridine ligands and the final platinum complexes is 1H NMR with particular analysis of the aromatic region of the spectra (7-9 ppm). The platinum complexes have potential application as anticancer agents and the synthesis method can be modified to produce trinuclear and other multinuclear complexes with different hydrogen bonding functionality in the bridging ligand.

This protocol describes the use of amide coupling reactions of isonicotinic acid and diaminoalkanes to form bridging ligands suitable for use in the synthesis of multinuclear platinum complexes, which combine aspects of the anticancer drugs BBR3464 and picoplatin.

Amide coupling reactions can be used to synthesize bispyridine-based ligands for use as bridging linkers in multinuclear platinum anticancer drugs. ...

A Method to Manipulate Surface Tension of a Liquid Metal via Surface Oxidation and Reduction

Controlling interfacial tension is an effective method for manipulating the shape, position, and flow of fluids at sub-millimeter length scales, where interfacial tension is a dominant force. A variety of methods exist for controlling the interfacial tension of aqueous and organic liquids on this scale; however, these techniques have limited utility for liquid metals due to their large interfacial tension.
Liquid metals can form soft, stretchable, and shape-reconfigurable components in electronic and electromagnetic devices. Although it is possible to manipulate these fluids via mechanical methods (e.g., pumping), electrical methods are easier to miniaturize, control, and implement. However, most electrical techniques have their own constraints: electrowetting-on-dielectric requires large (kV) potentials for modest actuation, electrocapillarity can affect relatively small changes in the interfacial tension, and continuous electrowetting is limited to plugs of the liquid metal in capillaries.
Here, we present a method for actuating gallium and gallium-based liquid metal alloys via an electrochemical surface reaction. Controlling the electrochemical potential on the surface of the liquid metal in electrolyte rapidly and reversibly changes the interfacial tension by over two orders of magnitude ( &#820;500 mN/m to near zero). Furthermore, this method requires only a very modest potential (&#60; 1 V) applied relative to a counter electrode. The resulting change in tension is due primarily to the electrochemical deposition of a surface oxide layer, which acts as a surfactant; removal of the oxide increases the interfacial tension, and vice versa. This technique can be applied in a wide variety of electrolytes and is independent of the substrate on which it rests.

We present a method to control the interfacial energy of a liquid metal in an electrolyte via electrochemical deposition (or removal) of a surface oxide layer. This simple method can control the capillary behavior of gallium-based liquid metals by tuning the interfacial energy rapidly, significantly, and reversibly using modest voltages.

Controlling interfacial tension is an effective method for manipulating the shape, position, and flow of fluids at sub-millimeter length scales, where ...

Synthesis and Characterization of Supramolecular Colloids

Control over colloidal assembly is of utmost importance for the development of functional colloidal materials with tailored structural and mechanical properties for applications in photonics, drug delivery and coating technology. Here we present a new family of colloidal building blocks, coined supramolecular colloids, whose self-assembly is controlled through surface-functionalization with a benzene-1,3,5-tricarboxamide (BTA) derived supramolecular moiety. Such BTAs interact via directional, strong, yet reversible hydrogen-bonds with other identical BTAs. Herein, a protocol is presented that describes how to couple these BTAs to colloids and how to quantify the number of coupling sites, which determines the multivalency of the supramolecular colloids. Light scattering measurements show that the refractive index of the colloids is almost matched with that of the solvent, which strongly reduces the van der Waals forces between the colloids. Before photo-activation, the colloids remain well dispersed, as the BTAs are equipped with a photo-labile group that blocks the formation of hydrogen-bonds. Controlled deprotection with UV-light activates the short-range hydrogen-bonds between the BTAs, which triggers the colloidal self-assembly. The evolution from the dispersed state to the clustered state is monitored by confocal microscopy. These results are further quantified by image analysis with simple routines using ImageJ and Matlab. This merger of supramolecular chemistry and colloidal science offers a direct route towards light- and thermo-responsive colloidal assembly encoded in the surface-grafted monolayer.

A protocol for the synthesis and characterization of colloids coated with supramolecular moieties is described. These supramolecular colloids undergo self-assembly upon the activation of the hydrogen-bonds between the surface-anchored molecules by UV-light.

Control over colloidal assembly is of utmost importance for the development of functional colloidal materials with tailored structural and mechanical ...

Preparation and Reactivity of a Triphosphenium Bromide Salt: A Convenient and Stable Source of Phosphorus(I)

We present herein the optimized synthesis of a triphosphenium bromide salt. Apart from being a versatile metathesis reagent, this unusually stable low-valent-phosphorus-containing compound acts as a useful P+ transfer agent. Unlike traditional methods employed to access low-coordinate phosphorus species which usually require pyrophoric phosphorus-containing precursors (white phosphorus, Tris(trimethylsilyl)phosphine, etc.), or harsh reducing agents (alkali metals, potassium graphite, etc.), the current approach does not involve pyrophoric or explosive reagents and can be done on large scales (&#62;20 g) in excellent yields by undergraduates with basic air-free synthetic training. The bromide counter ion is readily exchanged with other anions such as tetraphenyl borate (described herein) using typical salt metathesis reagents to obtain materials with desired properties and reactivities. The versatility of this P+ transfer approach is exemplified by the reactions of these triphosphenium precursors with an N-heterocyclic carbene and an anionic bisphosphine, each of which readily displace the neutral bisphosphine to give an NHC-stabilized phosphorus(I) cation and a phosphorus(I) containing zwitterion, respectively.

Preparation and Reactivity of a Triphosphenium Bromide Salt: A Convenient and Stable Source of PhosphorusI

The synthesis of a triphosphenium bromide salt is described and its use as a P+ transfer agent is outlined by reactions with an N-heterocyclic carbene and an anionic bisphosphine, yielding an NHC-stabilized P(I) cation and a P(I) containing zwitterion, respectively.

We present herein the optimized synthesis of a triphosphenium bromide salt. Apart from being a versatile metathesis reagent, this unusually stable ...

Synthesis and Mass Spectrometry Analysis of Oligo-peptoids

Peptoids are sequence-controlled peptide-mimicking oligomers consisting of N-alkylated glycine units. Among many potential applications, peptoids have been thought of as a type of molecular information storage. Mass spectrometry analysis has been considered the method of choice for sequencing peptoids. Peptoids can be synthesized via solid phase chemistry using a repeating two-step reaction cycle. Here we present a method to manually synthesize oligo-peptoids and to analyze the sequence of the peptoids using tandem mass spectrometry (MS/MS) techniques. The sample peptoid is a nonamer consisting of alternating N-(2-methyloxyethyl)glycine (Nme) and N-(2-phenylethyl)glycine (Npe), as well as an N-(2-aminoethyl)glycine (Nae) at the N-terminus. The sequence formula of the peptoid is Ac-Nae-(Npe-Nme)4-NH2, where Ac is the acetyl group. The synthesis takes place in a commercially available solid-phase reaction vessel. The rink amide resin is used as the solid support to yield the peptoid with an amide group at the C-terminus. The resulting peptoid product is subjected to sequence analysis using a triple-quadrupole mass spectrometer coupled to an electrospray ionization source. The MS/MS measurement produces a spectrum of fragment ions resulting from the dissociation of charged peptoid. The fragment ions are sorted out based on the values of their mass-to-charge ratio (m/z). The m/z values of the fragment ions are compared against the nominal masses of theoretically predicted fragment ions, according to the scheme of peptoid fragmentation. The analysis generates a fragmentation pattern of the charged peptoid. The fragmentation pattern is correlated to the monomer sequence of the neutral peptoid. In this regard, MS analysis reads out the sequence information of the peptoids.

A protocol is described for the manual synthesis of oligo-peptoids followed by sequence analysis by mass spectrometry.

Peptoids are sequence-controlled peptide-mimicking oligomers consisting of N-alkylated glycine units. Among many potential applications, peptoids have ...

Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile N-(2-alkoxyvinyl)sulfonamides, which react under a variety of conditions to afford useful N- and O-containing compounds. Acid-catalyzed addition of alcohols or thiols to N-(2-alkoxyvinyl)sulfonamide-containing phthalans provides access to ketals and thioketals, respectively. Selective reduction of the vinyl group in N-(2-alkoxyvinyl)sulfonamide-containing phthalans via hydrogenation yields the corresponding phthalan in good yield, whereas reduction with sodium bis(2-methoxyethoxy)aluminumhydride generates a ring-opened phenethylamine analogue. Because the N-(2-alkoxyvinyl)sulfonamide functional group is synthetically versatile, but often hydrolytically unstable, this protocol emphasizes key techniques in preparing, handling, and reacting these pivotal substrates in several useful transformations.

Preparation of N-2-alkoxyvinylsulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Representative experimental procedures for the synthesis of N-(2-alkoxyvinyl)sulfonamides and subsequent conversion to phthalan and phenethylamine derivatives are presented in detail.

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile ...

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles

Bicyclic aziridinium ions were generated by the removal of an appropriate leaving group through internal nucleophilic attack by nitrogen atom in the aziridine ring. The utility of bicyclic aziridinium ions, specifically 1-azoniabicyclo[3.1.0]hexane and 1-azoniabicyclo[4.1.0]heptane tosylate highlighted in the aziridine ring openings by the nucleophile with the release of the ring strain to yield the corresponding ring-expanded azaheterocycles such as pyrrolidine, piperidine and azepane with diverse substituents on the ring in regio- and stereospecific manner. Herein, we report a simple and convenient method for the preparation of the stable 1-azabicyclo[4.1.0]heptane tosylate followed by selective ring opening via a nucleophilic attack either at the bridge or at the bridgehead carbon to yield piperidine and azepane rings, respectively. This synthetic strategy allowed us to prepare biologically active natural products containing piperidine and azepane motif including sedamine, allosedamine, fagomine and balanol in highly efficient manner.

Bicyclic aziridinium ions such as 1-azoniabicyclo[4.1.0]heptane tosylate were generated from 2-[4-tolenesulfonyloxybutyl]aziridine, which was utilized for the preparation of substituted piperidines and azepanes via regio- and stereospecific ring-expansion with various nucleophiles. This highly efficient protocol allowed us to prepare diverse azaheterocycles including natural products such as fagomine, febrifugine analogue and balanol.

Bicyclic aziridinium ions were generated by the removal of an appropriate leaving group through internal nucleophilic attack by nitrogen atom in the ...

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine

Summary

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Chapters in this video

Template Directed Synthesis of Plasmonic Gold Nanotubes with Tunable IR Absorbance

Preparation of Silica Nanoparticles Through Microwave-assisted Acid-catalysis

Preparation of Hydrophobic Metal-Organic Frameworks via Plasma Enhanced Chemical Vapor Deposition of Perfluoroalkanes for the Removal of Ammonia

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents

A Method to Manipulate Surface Tension of a Liquid Metal via Surface Oxidation and Reduction

Synthesis and Characterization of Supramolecular Colloids

Preparation and Reactivity of a Triphosphenium Bromide Salt: A Convenient and Stable Source of Phosphorus(I)

Synthesis and Mass Spectrometry Analysis of Oligo-peptoids

Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles