Melissa Peretich1872 Campus Delivery
Fort Collins, 80523
(970) 491-6668
E-mail me at:
peretimi@lamar.colostate.edu
Numerous antitumor antibiotics containing a piperizinohydroisoquinoline motif have been isolated and consequently have attracted synthetic attention.¬1 One of these compounds, cribrostatin IV (1), a neoplastic agent, was isolated from a blue marine sponge Cribrochalina in reef passages in the Republic of Maldives.2 Shortly after the isolation of cribrostatin IV (1), Kubo and coworkers reported a reassignment of reneiramycin H, identifying it to be identical to 1.3,4 Cribrostatin IV is closely related to other members of the renieramycins, of the saframycins, and most notably, Ecteinascidin 743 (Et)-743, which was demonstrated to be a highly promising, exceedingly potent antitumor agent currently in phase II/II clinical trials. Consistent with other compounds in this class, cribrostatin IV (1) has also displayed potent biological activities.
Our interest in the total synthesis of 1 as well as related compounds arose from an unexpected synthetic opportunity afforded by studies directed toward the synthesis of bioxalomycin.5 Specifically, attempts to open the β-lactam substructures contained within intermediates employed in the route led to elimination products that possessed similar structural features 1. The retrosynthetic analysis, shown below, is currently being employed for the synthesis of 1.
References
(1) For a review, see: Scott, J. D.; Williams, R. M. Chemistry and Biology of the Tetrahydroisoquinoline Antitumor Antibiotics. Chem. Rev. 2002, 102, 1669-1730.
(2) Pettit, G. R.; Knight, J. D.; Collins, J. C.; Herald, D. L.; Pettit, R. K.; Boyd, M. R.; Young, V. G. Antineoplastic Agents 430. Isolation and Structure of Cribrostatins 3, 4, and 5 from the Republic of Maldives Cribrochalina Species. J. Nat. Prod. 2000, 63, 793-798.
(3) Parameswaran, P. S.; Naik, C. G.; Kamat, S. Y. Renieramycins H & I, Two Novel Alkaloids from the Sponge Haliclona Cribricutis DENDY. Indian J. Chem. 1998, 37B, 1258.
(4) Saito, N.; Sakai, H.; Suwanborirux, K.; Pummangura, S.; Kubo, A. 13C NMR Spectral Assignment of 5-Hydroxy-1,5-Imino-3-Benzazocin-4,7,10-Trione Derivatives: The Revised Structure of Renieramycin H. Heterocycles 2001, 55, 21.
(5) Herberich, B.; Vazquez, A.; Kinugawa, M.; Jin, W.; Williams, R. M. Sequential Staudinger/Pictet-Spengler Cyclization Reactions for the Construction of Densely Functionalized Tetrahydroisoquinolines. Tetrahedron Lett. 2001, 42, 543-546.