| Abstract
| - OSW saponins, featuring a 16β,17α-dihydroxycholest-22-one aglycon and an acylated β-d-xylopyranosyl-(1→3)-α-l-arabinopyranosyl residue attached to the 16-hydroxyl group, have recentlybeen discovered from a group of lily plants, which show potent antitumor activities with a novelmechanism of action. This paper describes an aldol approach to the stereoselective construction ofthe 16α,17α-dihydroxycholest-22-one structure from 16α-hydroxy-5-androsten-17-ones and propionates. Elaboration of the aldol adducts toward OSW-1, involving installation of the isoamyl ketoneside chain, inversion of the 16-hydroxyl configuration, and selective protection of the C22-oxyfunction, has been explored and accomplished. In particular, the present route was found convenientfor the synthesis of OSW saponin analogues with a C22-ester side chain. Thus, the 23-oxa-analogueof OSW-1 (40) was prepared starting from the industrial dehydroisoandrosterone (1) in a lineareight-step sequence and in 26% overall yield. Analogues with a variety of modified side chainswere prepared, via aldol condensation with propionates of varying length, thiopropionate, andacetate (for preparation of 68−75) or via aminolysis of the 22,16-lactone 26 (for preparation of the23-N-analogues). Cross metathesis (CM) reaction was also found feasible for modification at thefinal stage from C22-allyl ester 70. Valuable structure−activity relationships (SAR), together withthe practical synthetic approach, have thus been provided to set a new stage for further studies onthis new type of antitumor structures.
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