Epoxides bryostatins

Chiral Pool Reagent. (7 )-Pantolactone has been used as a source of chiral fragments for synthesis. Applications include use in the syntheses of the elfamycins (eq 12) and the bryostatins (eq IS). It has also been used to prepare potentially useful chiral epoxide synthons possessing a quaternary gem-dimethyl carbon. ... 

The stereocontrolled enantioselective synthesis of an advanced B-ring synthon of bryostatin 1 was achieved in the laboratory of K.J. Hale. " The key step was a Smith-Tietze coupling of 2-lithio-2-TBS-1,3-dithiane with a homochiral epoxide in the presence of HMPA. The resulting dithiane alkoxide was trapped with TBSCI in situ followed by deprotection of the dithiane moiety to give a Crsymmetrical ketone. This ketone was then further elaborated into the target B-ring synthon. 

In the synthesis of the B ring of bryostatins. Hale et al. have treated epoxide 33, obtained from the alcohol 32, with a catalytic amount of cam-phorsulfonic acid and THP 34 was produced in 87% yield according to a 6-exo-tet ring closure (Scheme 19) (20000L2189). 

Parallel results were found when bryostatins 4 and 10 were allowed to react with m-chloroperbenzoic acid in methylene chloride at room temperature. Introduction of one oxygen atom required two days. The SP-SIMS spectra were consistent with an additional 16 mass units, but while epoxidation of bryostatin 4 occurred at the A -olefin, epoxidation of bryostatin 10 occurred at the A -olefin, a conclusion reached by considering the H-NMR spectra. The spectrum of bryostatin 10 epoxide retained the olefinic resonances of the A double bond but the H-30 olefinic resonance at 85.658 was shifted to higher field at 53.358, a shift characteristic of hydrogen on an epoxide. In addition, the C-36 methyl... 

Scheme 29 Brpnsted acid-catalyzed epoxide opening to the B ring of the bryostatins [58]...

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