서지주요정보
Synthese of key intermediates to 1β-methylcarbapenem antibiotics = 항생제 1β-메틸카바페넴을 위한 중요 중간체의 합성에 관한 연구
서명 / 저자 Synthese of key intermediates to 1β-methylcarbapenem antibiotics = 항생제 1β-메틸카바페넴을 위한 중요 중간체의 합성에 관한 연구 / Hee-Seung Lee.
저자명 Lee, Hee-Seung ; 이희승
발행사항 [대전 : 한국과학기술원, 1996].
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등록번호

8006655

소장위치/청구기호

학술문화관(문화관) 보존서고

DCH 96006

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초록정보

A highly enantioselective synthesis of the key intermediate 8 of 1β-methylcarbapenem antibiotics was accomplished. The retrosynthetic strategy was focused on setting four contiguous chiral centers in the bicyclic isoxazolidine 169, followed by selective N-O bond cleavage and ultimate cyclization to construct the β-lactam ring. The key features of the scheme include the intramolecular 1,3-dipolar cycloaddition of nitrone to a bicyclic isoxazolidine with complete control of stereocenters and β-lactam formation from the β-amino acid 206b with trifluoroacetic anhydride in the presence of triethylamine. The substrate for the 1,3-dipolar cycloaddition, trans-lactol 164a, was prepared in 4 steps in three reaction pots starting from methyl (R)-3-iodo-2-methylpropionate in 76% overall yield. It was subjected to the nitrone formation with N-p-methoxybenzylhydroxylamine followed by the intramolecular 1,3-dipolar cycloaddition to provide the bicyclic isoxazolidine 169 as a single isomer with correct stereochemistry in 89% overall yield. Swern oxidation of 169, enol ether formation and oxidative cleavage followed by Wadsworth-Emmons olefination provided the conjugated ester 204a in 69% overall yield. Reductive N-O bond cleavage of 204a, β-lactam formation, debenzylation, TBS protection and oxidative cleavage in sequence afforded the desired azetidinone 8 in 74% overall yield from 204a. The direct formation of β-keto ester 181 from 209b, d, not via carboxylic acid 8, was attempted by palladium catalyzed oxidation. However, allyl ester 209b and p-methoxybenzyl ester 209d could not be converted into the desired β-keto esters. An alternative route to obtain the β-keto acid 232 from bicyclic ketone 184 was also intended. Ketone 184 was converted into 227b over 9 steps, of which the phenyl substituent was found to be resistant to oxidative degradation into carboxylic acid group.

서지기타정보

서지기타정보
청구기호 {DCH 96006
형태사항 iii, 169 p. : 삽도 ; 22 cm
언어 영어
일반주기 Includes appendix
저자명의 한글표기 : 이희승
지도교수의 영문표기 : Sung-Ho Kang
지도교수의 한글표기 : 강성호
수록 잡지명 : "An asymmetric synthesis of a key intermediate to 1β-methylcarbapenem antibiotics". Tetrahedron Letter. Elsevier Science Ltd., vol. 36, no. 37, pp. 6713-6716 (1995)
학위논문 학위논문(박사) - 한국과학기술원 : 화학과,
서지주기 Reference : p. 132-140
주제 β-Methylcarbapenem
1,3-Dipolar Cycloaddition
β-lactam Antibiotics
β-메틸카바페넴
1,3-이중극성 고리화첨가반응
β-락탐 항생제
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