Corticatic Acids D and E, Polyacetylenic Geranylgeranyltransferase Type I Inhibitors, from the Marine Sponge Petrosia corticata

Abstract

Two new polyacetylenic acids, corticatic acids D (2) and E (3), have been isolated from the marine sponge Petrosia corticata along with the known corticatic acid A (1) as geranylgeranyltransferase type I (GGTase I) inhibitors. Their structures were elucidated on the basis of spectroscopic and chemical methods. Compounds 1-3 inhibited GGTase I from Candida albicans with IC(50) values of 1.9-7.3 microM.

Biosynthesis and function of polyacetylenes and allied natural products

“…35) [339]. 31A and the related acids D and E (31D-E) have potential as selective antifungal agents as they were found to inhibit yeast geranylgeranyltransferase type 1, which has only 30% sequence homology to the human enzyme [340]. Acids 31A-C bear great resemblance to the petrocortynes when compared at the C1-ends, but differ in the locations of the internal unsaturation (C-17 to C-20).…”

First Stereoselective Total Synthesis of Gallicynoic Acids G and H

“…The reaction was quenched by addition of MeOH (0.3 ml) and stirring was continued for another 10 min. After the addition of NH 4 Cl soln., the mixture was extracted with Et 2 O (3 Â 7 ml), the combined org. phase dried (Na 2 SO 4 ) and concentrated, and the residue purified by CC (hexane/AcOEt 98 : 2): 13a (0.23 g, 94%).…”

“…Reduction of 9 with LiAlH 4 [15b] gave stereochemically pure (E)-alkenol 10 in 90% yield. Sharpless asymmetric epoxidation of 10 ((À)-diisopropyl tartrate (DIPT), ( i PrO) 4 Ti, cumene hydroperoxide (CHP), À 208) furnished (2R,3R)-oxiranemethanol 11 [16], which on subsequent reaction with Ph 3 P in CCl 4 in the presence of The construction of the basic C-atom skeleton of the gallicynoic acids 1 and 2 (Scheme 3) was achieved by the alkynylation reaction [17] of the known aldehyde 6 or 7, respectively, with the (silyloxy)alkyne 5. The alkynol 13 (or 14, resp.)…”

Structural reappraisal of corticatic acids, biologically active linear polyacetylenes, from a marine sponge of the genus Petrosia

“…Corticatic acid A (2) was first isolated from the marine sponge Petrosia corticata as antifungal metabolite [6], and was later rediscovered from the same species of the sponge as a geranylgeranyltransferase inhibitor [7]. Several congeners were also isolated from P. corticata [6,7].…”

“…Several congeners were also isolated from P. corticata [6,7]. The three functionalized units in corticatic acid A were initially connected through C 5 and C 11 methylene chains on the basis of 2D nuclear magnetic resonance (NMR) data [6].…”