Stereoselective acylation of the E,E-vinylketene silyl N,O-acetal and its application to the synthesis of khafrefungin.

Stereoselective acylation of the E,E-vinylketene silyl N,O-acetal possessing a chiral auxiliary has been achieved by using acid anhydrides and SnCl4. Acid anhydrides having alkyl chains gave the adducts in excellent stereoselectivity. The formal synthesis of khafrefungin has been accomplished by the methodology.

syn-Selective Kobayashi aldol reaction using acetals.

The Kobayashi aldol reaction has been used to construct anti-aldol products by remote stereoinduction. Since the product of the Kobayashi aldol reaction has a typical polyketide structure, this reaction has been applied to the total synthesis of natural products. By varying this reaction, it was found that the reaction with acetals in the presence of Lewis acid proceeded to give syn adducts in high stereoselectivity. This is the first example of the stereoselective reaction of the chiral dienol ether and acetals.

Concise synthesis of reduced propionates by stereoselective reductions combined with the Kobayashi reaction.

A concise and straightforward synthesis of 2,4,6-trimethyloctanoates was established by using the sequence of the vinylogous Mukaiyama aldol reaction and regio- and stereoselective reduction reactions. All isomers were obtained selectively in a few steps. The short step synthesis of septoriamycin A, an antimalarial and antileishmanial agent, has been achieved by this methodology.

Syn-selective Kobayashi aldol reaction using the E,E-vinylketene silyl N,O-acetal.

The Kobayashi aldol reaction is one of the most powerful methods to synthesize the polyketide skeleton and has been applied to the total synthesis of natural products. This methodology has been used to construct anti-aldol products, and only a few precedents on the syn-selective Kobayashi aldol reaction are known. A syn-selective Kobayashi aldol reaction by using the E,E-vinylketene silyl N,O-acetal and an excess amount of Lewis acid is presented.