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Volumn 65, Issue 11, 2009, Pages 2244-2253

Efficient synthesis and biological activity of enantiomeric pairs of thiolactomycin and its 3-demethyl derivative

Author keywords

Antibiotic; Deconjugative asymmetric sulfenylation; Inhibitor of fatty acid synthase

Indexed keywords

3 DEMETHYL DERIVATIVE; 3,3 DIMETHOXYPROPYL METHANETHIOSULFONATE; OXAZOLIDINE DERIVATIVE; SULFONIC ACID DERIVATIVE; THIOLACTOMYCIN; UNCLASSIFIED DRUG;

EID: 59749095838     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tet.2009.01.054     Document Type: Article
Times cited : (10)

References (43)
  • 1
    • 59749096021 scopus 로고    scopus 로고
    • Parts of this study have been the subjects of two preliminary communications
    • Parts of this study have been the subjects of two preliminary communications:
  • 22
    • 59749086999 scopus 로고    scopus 로고
    • note
    • In the preliminary experiments, (R)-4-isopropyloxazolidin-2-one (i), (S)-4-isopropyl-thiazolidin-2-thione (ii), and (1R)-2,10-camphur-sultam (iii) were examined as chiral auxiliaries in addition to (R)-4-benzyloxazolidin-2-one. However, when i was employed as a chiral source, the deconjugative asymmetric α-sulfenylation usually took place with a decreased diastereoselectivity and in a lower chemical yield than those obtained using (R)-4-benzyloxazolidin-2-one. In the case where ii was used as a chiral source, the attempted asymmetric reaction under various conditions always gave complex mixtures of the products. The asymmetric reaction employing iii as a chiral source afforded the ε-sulfenylated product corresponding to 11 (see text) as a sole product. Based on these numerous experiments, (R)-4-benzyloxazolidin-2-one was selected as the most promising chiral auxiliary. Ohata, K.; Terashima, S., unpublished results.
  • 23
    • 59749086474 scopus 로고    scopus 로고
    • note
    • 4p-Me) underwent deconjugative asymmetric α-sulfenylation to give α-sulfenylated products in 84% and 53% yield, respectively, the methylsulfenyl and the (2-trimethylsilyl)ethylsulfenyl group introduced into the reaction products could not be elaborated to a thiol or an acylsulfenyl group. Ohata, K.; Terashima, S., unpublished results.{A figure is presented}
  • 25
    • 59749088474 scopus 로고    scopus 로고
    • note
    • At the design stage for this synthetic strategy, it was uncertain whether 7 or ent-7 should be selected to produce the desired 5. However, it was expected that 5 could be obtained as a major product by selecting a chiral auxiliary and by tuning the conditions for reaction.
  • 26
    • 0345304282 scopus 로고    scopus 로고
    • Deconjugative asymmetric allylation of a dienolate with formation of a quaternary asymmetric center was recently reported by Kobayashi, et al.
    • Deconjugative asymmetric allylation of a dienolate with formation of a quaternary asymmetric center was recently reported by Kobayashi, et al. Abe T., Suzuki T., Sekiguchi K., Hosokawa S., and Kobayashi S. Tetrahedron Lett. 44 (2003) 9303-9305
    • (2003) Tetrahedron Lett. , vol.44 , pp. 9303-9305
    • Abe, T.1    Suzuki, T.2    Sekiguchi, K.3    Hosokawa, S.4    Kobayashi, S.5
  • 33
    • 59749103965 scopus 로고    scopus 로고
    • note
    • In our preliminary experiments, Dieckmann condensation of the imide compound derived from 5 by sequential deacetalization, retro-Michael reaction, and acylation without transesterification were attempted to produce 1. However, since the leaving ability of the imide moiety toward nucleophilic attack of the α-carbanion of thioester was insufficient for Dieckmann condensation under various conditions, we decided to subject the corresponding ester 3, which had a leaving ability superior to that of the imide compound, to Dieckmann condensation.
  • 34
    • 59749097466 scopus 로고    scopus 로고
    • note
    • In addition to benzyl ester 15, some other esters (methyl, ethyl, and isopropyl ester) were synthesized in a similar manner. Since the thiols derived from these esters by sequential deacetalization and retro-Michael reaction were fairly volatile and unstable, the chemical yield of the acylated compound carrying a methyl, ethyl or isopropyl ester was found to be lower than that for 3 bearing a benzyl ester.
  • 35
    • 59749091116 scopus 로고    scopus 로고
    • note
    • 1H NMR spectrum (see Experimental).
  • 36
    • 59749102046 scopus 로고    scopus 로고
    • note
    • 3 as an alkali metal base. However, all these bases were found to be not effective for this retro-Michael reaction.
  • 38
    • 59749093038 scopus 로고    scopus 로고
    • note
    • Determination of MICs by agar dilution methods was performed according to the guideline M7-A6 of the Clinical and Laboratory Standards Institute (2003).


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.