Total synthesis of (+)- and (-)-duryne: a potent anticancer agent from the marine sponge Cribrochalina dura. Establishment of the central double bond geometry and the absolute configuration of the chiral centers.
Duryne is a C30 polyacetylenic alcohol with C2 symmetry. Despite its potent cytotoxicity, its central double bond geometry and the absolute configuration of the chiral centers were not determined. We report the total syntheses of both enantiomers of the anticancer natural product (+)-duryne and the establishment of its stereochemistry by synthesizing both geometric isomers. The natural (+)-duryne is identified as (15Z) and (3S,28S) as shown in structure 1. The autoxidation/Wittig coupling reaction was employed to synthesize the central (Z)-olefin. The stereochemistry of the (E)-alkene isomer was constructed stereoselectively by using LiAlH4 reduction of the corresponding alkyne. The absolute configurations of the chiral centers are established by using Burgess' enzymatic resolution procedure with Pseudomonas AK lipase.
Gung
Benjamin W
BW
Department of Chemistry & Biochemistry, Miami University, Oxford, Ohio 45056, USA. gungbw@muohio.edu
Omollo
Ann O
AO
D000114:Acetylene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000438:Alcohols / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001688:Biological Products / Q000737:chemistry; D008968:Molecular Conformation; D009792:Oceans and Seas; D053279:Polyynes; D011161:Porifera / Q000737:chemistry*; D013237:Stereoisomerism
D000438:Alcohols; D000970:Antineoplastic Agents; D001688:Biological Products; C527593:duryne; D053279:Polyynes; D000114:Acetylene