Synthesis Of C1-C10and C17-C24Fragments Of Spirastrellolide A

Spirastrellolide A was a macrolide isolated from the Caribbean marine spongeSpirastrellolide coccinea by Andersen and co-works in2003. In addition to it′santimitotic effect, it represents a potential therapeutic agents for the treatment ofcancer as well as various neurological and metabolic disorders. As a result, thisnatural product has attracted an elegant array of synthetic efforts. We becameinterested in spirastrellolide A as a result of our recent interest and efforts indeveloping an unconventional approach to the synthesis of spiroketals. With low-coststating material and classic reaction type, we describe a synthetic approach towardsC1-C10and C11-C24fragment of Spirastrellolide A.Our synthesis commenced with1,5-pentanediol, which was quickly transformedinto an aldehyde via mono-benzylation and Swern oxidation. HEW-Modified Wittigolefination, followed by Dibal-H reduction, sets up the key allyl alcohol prepared forthe Sharpless asymmetric epoxidation. After ring-opening, SO3.Pyr. oxidation, Wittigreaction and acid catalyst O-1,4addition, to complete the pyran synthesis.In the second part, our synthesis of lactone commenced with L-arabinose. Byprotection of the hydroxyl groups, Dess-Martin oxidation, Wittig olefination and esterexchange, getting the lactone fragment. With this fragment in hand, we explored amodel reaction about synthsis of C11-C24fragment depending on our previous efforts.The main advantages of this method include low-cost starting material, mild reactionconditions and good functional group tolerance.We described the synthetic routes of C1-C10and C11-C24fragments ofSpirastrellolide A, making preparation for the total synthsis of the natural product.