서지주요정보
Synthetic studies on MR304A : a synthetic route to loracarbef : MR304의 합성연구 : 로라카르베프의 합성방법 : 진통제 캡사이신노이드와 항암제 클로린의 개발
서명 / 저자 Synthetic studies on MR304A : a synthetic route to loracarbef : development of analgesic capsaicinoids and antitumor chlorins = MR304의 합성연구 : 로라카르베프의 합성방법 : 진통제 캡사이신노이드와 항암제 클로린의 개발 / Jong-Cheol Lee.
저자명 Lee, Jong-Cheol ; 이종철
발행사항 [대전 : 한국과학기술원, 2001].
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등록번호

8012488

소장위치/청구기호

학술문화관(문화관) 보존서고

DCH 01016

SMS전송

도서상태

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초록정보

An attempted synthesis of MR304A 1 [1-(1,2,5-trihydroxy-3-isocyanopent-3-enyl)ethanol] was carried out. Cyclopentenone 3 was set as a key intermediate for the synthesis of 1. By the Honner-Emmons reaction, phosphonate 4 was expected to be synthesized 3, however, the reaction of lithium diethyl methylphosphonate with nitrile 18 and aldehyde 20 was unsuccessful. Samarium diiodide promoted pinacolic coupling reaction of dicarbonyl intermediate was ambitioned as an alternative way. The keto aldehyde 48 was obtained by the sequential treatment of aldehyde 36. The intramolecular carbonyl-coupling reaction of keto aldehyde 48 using samarium diiodide did not proceed cleanly. Cis-(3S, 4R) azetidinone, a key intermediate of Loracarbef, was the target molecule of our synthetic study. For the construction of the cis-substituted azetidinone, the intramolecular cyclization of β-amino acid was attempted. Stereoselective iodoamidation of Z-olefinic allylic alcohol 96 gave the aziridine 114. The regioselective ring opening of 114 with azide furnished α-azido-β-tosylamide ester 117a. Surprisingly, the various deprotection conditions of tosyl group of 117a were fruitless. Alternatively, Sharpless asymmetric aminohydroxylation of α,β-un- saturated ester 144a followed by introduction of azide afforded the α-azido-β-t-butylcarbamate ester 148. The intramolecular cyclization of 140 with Mukaiyama reagent afforded the required cis-substituted azetidinone 141. Introduction of phenoxy acetyl group and oxidation of primary alcohol furnished the desired β-lactam 91. N-Ayalkyl phenylacetamide, KR-25018 167 developed at KRICT, was proved to be a very potent analgesic agent with decreased pungency compared to capsaicin. By structural modification, we tried to improve the therapeutic index, i.e. enhanced analgesic activity, low toxicity and side effects, of phenylacetamides. A systematic replacement of the 3-position of N-aralkylphenylacetamide was performed. Most of the compounds showed moderate analgesic activities compared to the potent capsaicinoids. The side effects were not observed near the dose of $ED_{50}$. Furthuermore, conformational constriction by cyclization between phenyl ring and nitrogen of amide bond was performed. A new class of capsaicinoids, such as lactam 251 and benzazepine-3-one 258, were also prepared. For the development of the new generation photosensitizer for photodynamic therapy(PDT), structural variation of chlorin[methyl pheo- phorbide a(MPa) 296 and methyl pyropheophorbide a(MPPa) 297] was achieved. Several chlorin-fullerene dyads (300, 301, 307, 308 and Zn(II) metallated dyads) were prepared. The Vilsmeier reaction of nickel(II) MPPa 323 and Ni(II) purpurinimide 336 gave the nickel(II)-20-(2-formylvinyl)MPPa and 20-(2-formylvinyl)purpurinimide 337, respectively. A considerable bathochromic shift in major absorption band of 325 and 337 suggested them set as new lead compounds for PDT. The reaction of aldehyde 351 with fullerene$(C_{60})$ gave the pyrrolidine linked porphyrin-chlorin-fullerene triad 352 as a new fullerene based triads for a model of artificial photosynthetic reaction center as well as photosensitizer.

서지기타정보

서지기타정보
청구기호 {DCH 01016
형태사항 iv, 137 p. : 삽도 ; 26 cm
언어 영어
일반주기 저자명의 한글표기 : 이종철
지도교수의 영문표기 : Sung-Ho Kang
지도교수의 한글표기 : 강성호
수록잡지명 : "An asymmetric aminohydroxylation approach to the stereoselective synthesis of cis-substituted azetidinone of loracarbef". Tetrahedron letters, v. 42 no. 27, pp, 4519-4521 (2001)
학위논문 학위논문(박사) - 한국과학기술원 : 화학과,
서지주기 Reference : p. 132-137
주제 Loracarbef
capsaicinoids
Chlorins
MR304
analgesic
로라카르베프
캡사이신노이드
클로린
진통제
멜라닌 합성저해제
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