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The novel pentacyclic polyhydroxylated sterol, xestobergsterol A 1a , a strong inhibitor of histamine release from rat mast cells induced by anti-IgE, has been synthesized in 24 steps and good overall yield from stigmasterol 7 . The Breslow remote functionalization process has been extended to several more highly functionalized steroid derivatives, especially those with oxygen functionality in the B-ring. The key steps of the synthesis of xestobergsterol A 1a and its analogues, 7-deoxyxestobergsterol A 1d and 16,23- seco -23-deoxyxestobergsterol A 73 , are the Breslow remote functionalization of oxygenated steroids and for compounds 1a and 1d , a novel base-catalyzed epimerization-aldol condensation of a dione to give the desired CD- cis ring structure of the xestobergsterols. Thus the known alcohol 75 , prepared from stigmasterol 7 , was taken to the tetraacetate 107 which was then converted via a Breslow remote functionalization into the alkene aldehyde 114 which was transformed in 5 steps to xestobergsterol A 1a . Testing of the synthetic materials showed that the two analogues, 7-deoxyxestobergsterol A 1b and 16,23- seco -23-deoxyxestobergsterol A 73 , are also potent inhibitors of histamine release with IC 50 values (IC 50 500 nM and 750 nM, respectively) being only 1015 times less than that of xestobergsterol A itself (50 nM).

A novel pentacyclic polyhydroxylated sterol, xestobergsterol A (1a), has been synthesized in 24 steps and in good overall yield from stigmasterol 17. The key steps of the synthesis are the Breslow remote functionalization of the polyoxygenated steroid derived from 25 and the base-catalyzed epimerization−aldol condensation of the dione derived from 27.

The novel pentacyclic polyhydroxylated sterol, xestobergsterol A 1a , a strong inhibitor of histamine release from rat mast cells induced by anti-IgE, has been synthesized in 24 steps and good overall yield from stigmasterol 7 . The Breslow remote functionalization process has been extended to several more highly functionalized steroid derivatives, especially those with oxygen functionality in the B-ring. The key steps of the synthesis of xestobergsterol A 1a and its analogues, 7-deoxyxestobergsterol A 1d and 16,23- seco -23-deoxyxestobergsterol A 73 , are the Breslow remote functionalization of oxygenated steroids and for compounds 1a and 1d , a novel base-catalyzed epimerization-aldol condensation of a dione to give the desired CD- cis ring structure of the xestobergsterols. Thus the known alcohol 75 , prepared from stigmasterol 7 , was taken to the tetraacetate 107 which was then converted via a Breslow remote functionalization into the alkene aldehyde 114 which was transformed in 5 steps to xestobergsterol A 1a . Testing of the synthetic materials showed that the two analogues, 7-deoxyxestobergsterol A 1b and 16,23- seco -23-deoxyxestobergsterol A 73 , are also potent inhibitors of histamine release with IC 50 values (IC 50 500 nM and 750 nM, respectively) being only 1015 times less than that of xestobergsterol A itself (50 nM).

An enantiospecific synthesis of structure 1, previously assigned to the antitubercular marine natural product pseudopteroxazole, has been accomplished as outlined in Scheme 1. Coupling of diene acid 3 and amino phenol 4 produced the amide 5, which was subjected to a novel oxidative intramolecular Diels−Alder reaction to generate the tricyclic lactam 6a stereoselectively. This product was transformed via intermediates 7−11 into the diene 13. Cationic cyclization of 13 afforded two diastereomeric tricyclic amphilectanes which were separated and transformed by parallel four-step sequences into 1 and 2, respectively. Neither 1 nor 2 were identical with pseudopteroxazole, indicating a need for revision of the structure, probably to 16.

An enantiospecific synthesis of structure 1, previously assigned to the antitubercular marine natural product pseudopteroxazole, has been accomplished as outlined in Scheme 1. Coupling of diene acid 3 and amino phenol 4 produced the amide 5, which was subjected to a novel oxidative intramolecular Diels−Alder reaction to generate the tricyclic lactam 6a stereoselectively. This product was transformed via intermediates 7−11 into the diene 13. Cationic cyclization of 13 afforded two diastereomeric tricyclic amphilectanes which were separated and transformed by parallel four-step sequences into 1 and 2, respectively. Neither 1 nor 2 were identical with pseudopteroxazole, indicating a need for revision of the structure, probably to 16.

Revised structures are proposed for pseudopterosin G-J aglycon and helioporin E.

Thermolysis of the 3,5-hexadienyl acrylates (a) proceeds via the transition state E in which the connecting chain adopts a boatlike conformation due to a preference for maintaining ester overlap to afford the products b with good diastereoselectivity.