Onchidin B: A New Cyclodepsipeptide from the Mollusc Onchidium sp.
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- 作者：Rogelio Ferná ; ndez ; Jaime Rodrí ; guez ; Emilio Quiñ ; oá ; Ricardo Riguera ; Luis Muñ ; oz ; Miryam Ferná ; ndez-Suá ; rez ; and Cé ; cile Debitus
- 刊名：Journal of the American Chemical Society
- 出版年：1996
- 出版时间：November 20, 1996
- 年：1996
- 卷：118
- 期：46
- 页码：11635 - 11643
- 全文大小：464K
- 年卷期：v.118,no.46(November 20, 1996)
- ISSN：1520-5126
文摘
Onchidin B (4) is a cyclic depsipeptideisolated from the pulmonate mollusc Onchidium sp. Itsstructurewas determined by extensive 2D-NMR, FABMS, tandem FAB MS/MS, selectivehydrolysis, and synthesis. It containsfour 
-amino acids [two units of N-methyl valine (MeVal),two units of proline (Pro)], four -hydroxy acids [two2-hydroxyisovaleric acids (Hiv), two 2-hydroxy-3-methylpentanoic acidmoieties (Hmp)] and two units of the new
-hydroxy acid: 3-hydroxy-2-methyloct-7-ynoic acid (Hymo)].Selective hydrolysis and direct comparison by chiralGC-MS with authentic samples of the -amino and -hydroxy acidsallowed us the assignment of the entire absolutestereochemistry of onchidin B. In this way, the -hydroxy acidswere found to be (S)-Hiv and(S,S)-Hmp, and the-amino acids (R)-proline, (S)-proline, and(R)-MeVal. In order to establish the absoluteconfiguration of the new-hydroxy acid, Hymo, its four possible stereoisomers werestereoselectively synthesized using chiralN-propionyloxazolidinones and hex-5-ynal as starting material. Comparison byHPLC-MS of the synthetic samples with thenatural Hymo (all derivatized as esters of(-)-(R)--methoxy--(9-anthryl)acetic acid),affirmed its absolutestereochemistry as (2R,3R). Thus, onchidin B(4) is cyclo[(R)-MeVal-(R,R)-Hymo-(S)-Pro-(S,S)-Hmp-(S)-Hiv-(R)-MeVal-(R,R)-Hymo-(R)-Pro-(S,S)-Hmp-(S)-Hiv].It is formed by a head-to-tail linkage of two halves, eachonebuilt by five units and identical sequence. The lack of symmetryof onchidin B is thus due to the presence of one(S)-Pro unit in one half and one (R)-Pro unit inthe other. The structural similarity between onchidin B(4) andonchidin (2), both isolated from the same organism, andbetween the -hydroxy acid Hymo (5) and the-aminoacid Amo (3) found in onchidin is noticed.
-amino acids [two units of N-methyl valine (MeVal),two units of proline (Pro)], four -hydroxy acids [two2-hydroxyisovaleric acids (Hiv), two 2-hydroxy-3-methylpentanoic acidmoieties (Hmp)] and two units of the new-hydroxy acid: 3-hydroxy-2-methyloct-7-ynoic acid (Hymo)].Selective hydrolysis and direct comparison by chiralGC-MS with authentic samples of the -amino and -hydroxy acidsallowed us the assignment of the entire absolutestereochemistry of onchidin B. In this way, the -hydroxy acidswere found to be (S)-Hiv and(S,S)-Hmp, and the-amino acids (R)-proline, (S)-proline, and(R)-MeVal. In order to establish the absoluteconfiguration of the new-hydroxy acid, Hymo, its four possible stereoisomers werestereoselectively synthesized using chiralN-propionyloxazolidinones and hex-5-ynal as starting material. Comparison byHPLC-MS of the synthetic samples with thenatural Hymo (all derivatized as esters of(-)-(R)--methoxy--(9-anthryl)acetic acid),affirmed its absolutestereochemistry as (2R,3R). Thus, onchidin B(4) is cyclo[(R)-MeVal-(R,R)-Hymo-(S)-Pro-(S,S)-Hmp-(S)-Hiv-(R)-MeVal-(R,R)-Hymo-(R)-Pro-(S,S)-Hmp-(S)-Hiv].It is formed by a head-to-tail linkage of two halves, eachonebuilt by five units and identical sequence. The lack of symmetryof onchidin B is thus due to the presence of one(S)-Pro unit in one half and one (R)-Pro unit inthe other. The structural similarity between onchidin B(4) andonchidin (2), both isolated from the same organism, andbetween the -hydroxy acid Hymo (5) and the-aminoacid Amo (3) found in onchidin is noticed.