Enantiomerically synthesis

Felpin, F.X., Girard, S., Vo-Thanh, G., Robins, R.f, ViUieras, L, Lebreton, L (2001) Efficient Enantiomeric Synthesis of PyrroUdine and Piperidine Alkaloids from Tobacco. Journal of Organic Chemistry, 66, 6305-6312. 

Scheme 19 Mechanism of enantiomeric synthesis of aryl oxazolidinones...

The results of enzymatic and antibacterial assays demonstrated that compound 165 (as a racemic mixture) exhibits activities similar to those of the parent oxazoline L-159,692 [103]. In order to identify the enantioselectiv-ity of this compound, the corresponding R and S enantiomers were separately synthesized from (R)- or (S)-3-(4-methoxyphenyl)-5-hydroxymethyl-4,5-dihydroisoxazole (166) according to the method of Ukaji et al. [107,108] and tested for LpxC inhibitory and antibacterial activities [103]. Interestingly, only the S enantiomer of 166 exhibited strong enzyme inhibitory and antibacterial activity, while the R enantiomer of L-159,692 was the active component. The enantiomeric synthesis of compound 165 is depicted in Scheme 33. 

C.-K. Lee, K. Y. Sim, and J. Zhu, Enantiomeric synthesis of polyhydroxylated indolizidine analogues related to castanospermine l-Deoxy-7-epicastanospermine and l,7-dideoxy-7-fluorocastanosper-mine, Tetrahedron, 48 (1992) 8541—8544. 

Separation of the enantiomeric products of a bioconversion by chromatographic or electrophoretic methods. These methods are well suited for enantiomeric synthesis. 

The oxazolidinone-substituted olefin Ic (Scheme 3) constitutes another fortunate substrate for the diastereoselective synthesis of a chiral dioxetane , which is of preparative value for the enantiomeric synthesis of 1,2 diols . For example, the photooxygenation of the enecarbamate Ic produces the asymmetric dioxetane 2c in >95% jt-facial diastereoselectivity. The attack of the O2 occurs from the jt face anti to the isopropyl... 

The enantiomeric synthesis of rranj-3,4-disubstituted tetrahydrothiophenes using a sulfur ylide cycloaddition has been reported <990L1667>. The sulfur ylide derived from the action of cesium fluoride on sulfide 111 underwent an asymmetric cycloaddition with chiral a,p-unsaturated camphorsultam amide 112 giving tetrahydrothiophene 113 (80% de). The configuration was confirmed by cleavage of the chiral auxiliary followed by reductive desulfurization with Raney-Ni which gave known carboxylic acid 114. 

This example outlines how RRM can be harnessed for the synthesis of novel alkaloids. It also illustrates the various factors that need to be considered when designing a synthesis to harness a particular strategy i.e. the enantiomeric synthesis of the RRM precursor. 

Wei, C.-C. Weigele, M., Enantiomeric Synthesis of 3-Amino-4-carbamoyloxymethyl-2-azetidinone-1-sulfate. U.S. 4,502,994,1985 (to Hoffinann-LaRoche). 

Kwon, D.Y., Hong, Y.J., and Yoon, S.H., Enantiomeric synthesis of (S)-2-methylbutanoic acid methyl ester, apple flavor, using lipases in organic solvent, J. Agric. Food Chem., 48, 524, 2000. 

Bashiardes et al. [94] described an intramolecular cydoaddition reaction of unprotected carbohydrates 126, involving a nitrone ylide dipole 127 derived from the 1-aldehydic position, and an co-olefinic moiety constructed from the 6-hydroxyl function (Scheme 11.32). In this enantiomeric synthesis of novel bicyclic oxazoli-dines bearing a quaternary bridgehead, 128, a comparative study was performed of classical heating conditions and microwave-assisted cydoaddition, both in the same reaction medium, aqueous ethanol. All the examples provided products in yields which were improved from approximately 60% to 90%, basically because of the cleaner reactions. The reaction times were reduced from 48 h to just 1 h. 

I- 2]7t Cycloaddition reactions too have found a place in azepine synthesis. In studies related to the enantiomeric synthesis of norsecurine <9UA5384>, intramolecular cycloaddition of the alkyne group in (168) to the oxazole ring, followed by loss of acetonitrile from the adduct, furnishes the tricyclic azepine (169), as shown in Equation (16), and 2,3,4,5-tetrahydro-7,8-bis(trifluoromethyl)-l/7-pyrido[2,3-i]azepine (171) is obtained by intramolecular [4 + 2]n cycloaddition of (170) followed by elimination of nitrogen <90CBi33>. 

An efficient enantiomeric synthesis of (-)-methyl jasmonate [16] and (-l-)methyl epijasmonate [17] has been reported. The procedure makes use of a chiral cyclopen-tanoid building block that can easily be prepared from tartaric acid by phosphorus ylid chemistry (75). Jasmonic acid was also prepared by mixed Kolbe electrolysis (76). Methyl 3-methyljasmonate was synthesized from methyl jasmonate via methyl 3,7-dehydrojasmonate (77). 

Chu CK, Beach JW, Jeong LS, Choi WB, Conner FI, Alves AJ, Schinazi RF. Enantiomeric synthesis of (+)-BCH189, (+)-(2S, 5R)-l-[2-hydroxymethyl)-l,3-oxathiolan-5-yl]cytosine from D-mannose and its anti-HIV activity. J Org Chem 1991 56 6503-6505. 

Sankaranarayanan, S., Sharma, A and Chattopadhyay, S. (2002) Synthesis of the 1,5-dimethylic chiron enantiomers, 3,7,11-trimethyldodec-lO-en-l-ol application to enantiomeric synthesis of tribolure and a marine fiitty add. Tetrahedron Asymmetry, 13,1373-1378. 

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