Bryostatins

Title: Bryostatins
Literature References: Family of seventeen biologically active macrolides, bryostatins 1 through 15, A and B. Isolated from the marine bryozoans, Bugula neritina, L. and related organisms. Protein kinase C activators. Isoln and structure of bryostatin 1, one of the most abundant of the series: G. R. Pettit et al., J. Am. Chem. Soc. 104, 6846 (1982). Large-scale isoln of 1: D. E. Schaufelberger et al., J. Nat. Prod. 54, 1265 (1991). Abs config of 1, 2 and 3: G. R. Pettit et al., J. Org. Chem. 56, 1337 (1991). 1H- and 13C- NMR analyses of 1: D. E. Schaufelberger et al., Magn. Reson. Chem. 29, 366 (1991). Approaches to synthesis: R. Roy et al., Chem. Commun. 1989, 1308; K. Ohmori et al., Tetrahedron Lett. 34, 4981 (1993). Total synthesis of 7: M. Kageyama et al., J. Am. Chem. Soc. 112, 7407 (1990). Conversion of 2 to 1: G. R. Pettit et al., Can. J. Chem. 69, 856 (1991). Pharmacodynamics: R. L. Berkow et al., Cancer Res. 53, 2810 (1993); C. Stanwell et al., Int. J. Cancer 56, 585 (1994). Clinical evaluation of 1 in advanced cancer: J. Prendiville et al., Br. J. Cancer 68, 418 (1993). Review of pharmacology: P. M. Blumberg, G. R. Pettit, "The Bryostatins, a Family of Protein Kinase C Activators with Therapeutic Potential", in New Leads and Targets in Drug Research, P. Krogsgaard-Larsen et al., Eds. (Munksgaard, Copenhagen, 1992) pp 273-285. Review of isolation, structure elucidation and biological activity: G. R. Pettit, Fortschr. Chem. Org. Naturst. 57, 153-195 (1991).
Derivative Type: Bryostatin 1
CAS Registry Number: 83314-01-6
Molecular Formula: C47H68O17
Molecular Weight: 905.03
Percent Composition: C 62.37%, H 7.57%, O 30.05%
Properties: Colorless crystals from methylene chloride/methanol, mp 230-235°. [a]D25 +34.1° (c = 0.044 in methanol). uv max (methanol): 233, 263 nm (e 25700, 28700). Relatively insol in water. Soly in ethanol >4000 mg/ml. LD50 in mice, rats (mg/kg): 0.038, 0.068 i.v. (Prendiville).
Melting point: mp 230-235°
Optical Rotation: [a]D25 +34.1° (c = 0.044 in methanol)
Absorption maximum: uv max (methanol): 233, 263 nm (e 25700, 28700)
Toxicity data: LD50 in mice, rats (mg/kg): 0.038, 0.068 i.v. (Prendiville)
Bucetin Buchu Bucillamine Bucindolol Buclizine

Skeletal formula of bryostatin 1

Bryostatins are a group of macrolide lactones first isolated in the 1960s by George Pettit from extracts of a species of bryozoan, Bugula neritina. The structure of bryostatin 1 was determined in 1982.[1] To date 20 different bryostatins have been isolated.[2] Bryostatins are a potent modulators of protein kinase C. They are currently under investigation as anti-cancer agents and as a memory enhancing agent.