Bryostatin chemistry

Mutter R, Wills M. Chemistry and clinical biology of the bryostatins. Bioorg Med Chem 2000 8(8) 1841-60. 

The chemistry of A. convoluta collected from other regions of the world has also been described and provides yet another example of geographical variability of secondary metabolites. The possible occurrence of bryostatins in A. convoluta from the Gulf of Mexico, has been previously discussed in Section 2.2.1. Since this investigation was directed towards discovering antineoplastlc constituents, the nonactive amathamides would not have been detected. In another recent examination of A. convoluta for secondary metabolites, a series of P-phenylethylamine related alkaloids has been found [32]. The... 

The sea covers almost three-quarters of the earth s surface and contains a broader genetic variation among species relative to the terrestrial environment (155,158).Althoughanum-ber of important molecules have been derived from marine sources, including arabinosyl nucleotides, didemnin B, and bryostatin 1, there has been an inadequate focus on this potentially chemically productive biosphere. Sea snails, often called "nature s combinatorial chemistry factories," produce a bewildering array of novel conotoxins active at mamma-... 

Aldol reactions are ubiquitous in synthetic organic chemistry to generate intermediates of antihypertensive dmgs and calcium antagonists. Chiral p-hydroxy carbonyl compounds can readily be converted to 1, i-syn and anfr-diols and amino alcohols, which are the building blocks in many natural products such as antibiotics and pheromones and in many biologically active compounds. Aldol products have successfully been converted to key synthetic intermediates of epithilone A and bryostatin 7. ... 

In studies related to the synthesis of bryostatin natural products, it was shown that stereocontrolled cyclizations could be achieved in silyl-terminated Prins cyclizations (Scheme 5). ° Thus, the syn-P-hydroxy allyl silane (13) reacts with propionaldehyde to provide the cw-2,6-disubstituted 4-alkylidenetetrahydropyran (14) in excellent yield and stereocontrol of the olefin geometry (>95 5). The chemistry was examined by DPT (density functional theory) calculations, which suggested that the cyclization step occurs through a chair-like structure (15). Stereocontrol of the exocyclic double bond is thought to be a consequence of steric and electronic effects, in particular maximization of -silyl stabilization of forming carbocation center (16). 

The bryostatins represent one of the medically most promising series of marine animal constituents presently known. Their discovery, chemistry and biology will be reviewed here beginning with a historical perspective. 

Kageyama, M., and S. Masamune Studies Toward the Total Synthesis of Bryostatin 7. 31st Symposium on the Chemistry of Natural Products, Nagoya, Japan, 1989, 227. 

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