Polyoxin J Gosh

Since the first synthesis of polyoxin J by Kuzuhara in 1973 several other total syntheses have been reported. This problem is based on the stereoselective and convergent total synthesis described by Gosh and co-workers in 1999.  

CH2CI2, -78 °C, 2 h OCH3 2. MCPBA, NaHCOg, CH2CI2. r.t.,12 h 

DIBAH reduction of 4 at -78 °C provides the corresponding trans-allylic alcohol. Successive epoxidation with meto-chloroperbenzoic acid (MCPBA) yields a single syn epoxide 5. The stereochemical assignment is proven by a second experiment using the asymmetric Sharpless epoxidation protocol. Both MCPBA and the Sharpless protocol using (-)-diethyl D-tartrate provided 5. 

Interestingly, MCPBA epoxidation of cis alcohol 16 affords a mixture of diastereomeric epoxides (55 45 mixture). Furthermore, protection of the allylic alcohol as TBS ether (17) and subsequent epoxidation results as well in hardly any stereochemical selectivity (53 47 mixture). With regard to these results it is suggested that the trans-allylic hydroxy group is effectively involved in directing the MCPBA epoxidation event. 

The azido group is introduced by a titanium-mediated nucleophilic opening of 2,3-epoxy alcohol 5 invented by Sharpless. In principle, nucleophilic attack at C-2 or C-3 is possible. 

The protected methyl glycoside 3 is converted to the corresponding aldehyde by Swern oxidation using oxalyl chloride activated DMSO. Further reaction with triethyl phosphonoacetate and sodium hydride -known as the Horner-Wadsworth-Emmons reaction - provides selectively the trans et /Tun saturated ester 4 in 72 % yield. This valuable alternative to the Wittig olefination protocol uses phosphonate esters as substrates which are readily available from alkyl halides and trialkyl phosphites via the Arbuzov rearrangement.9 co2Et Reaction of the phosphonate with a suitable base gives the 

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