The large-scale isolation of bryostatin 1 from Bugula neritina following current good manufacturing practices.

A novel process was designed for the large-scale isolation of bryostatin 1 from the bryozoan Bugula neritina L. in order to obtain multigram quantities of highly pure material for formulation studies, preclinical toxicology, and clinical trials in cancer patients. Multigram quantities of bryostatin 1 were obtained from a collection of approximately 10,000 gallons of wet animal. A phorbol dibutyrate (PDBu) receptor binding assay and hplc with photodiode array detection were used for the design, validation, and control of the isolation process.

Antineoplastic agents, 177. Isolation and structure of phyllanthostatin 6.

The isolation and structural elucidation of a new Phyllanthus glycoside, phyllanthostatin 6 [7], was summarized. Phyllanthostatin 6 [7] was isolated from the roots of Phyllanthus acuminatus (Euphorbiaceae) and was found to inhibit (ED50 = 0.35 micrograms/ml) growth of the murine P-388 lymphocytic leukemia cell line. Two other new constituents were shown to be didesacetylphyllanthostatin 3 [9] and descinnamoylphyllanthocindiol [10]. Structure determinations were achieved employing hrfabms and 2D-nmr spectroscopy. Application of an hplc separation technique to the Phyllanthus glycosides and development of a new isolation procedure for the major antineoplastic constituent, phyllanthoside [1], are also described.

Dereplication of phorbol bioactives: Lyngbya majuscula and Croton cuneatus.

Lyngbya majuscula and Croton cuneatus were used as prototypes for the dereplication of phorbol ester receptor binding activity using a combination of hplc-uv and online phorbol dibutyrate (PDBu) receptor binding and batch fractionation over either Si gel or diolbonded Si gel. Debromoaplysiatoxin was responsible for the bioactivity of Lyngbya, whereas a complex of potent phorbol esters was detected in C. cuneatus.

Isolation and structure of the cytostatic lignan glycoside phyllanthostatin A.

An unusual cytostatic (PS ED50 4 micrograms/ml) lignan ester has been isolated from the Central American tree Phyllanthus acuminatus and designated phyllanthostatin A [1]. Separation of an MeOH extract of the root by size exclusion chromatography, high speed counter-current distribution, and semipreparative hplc afforded glycoside 1 in 0.007% yield. In solution, phyllanthostatin A was slowly transformed into justicidin B [4]. The structure of lignan glycoside 1 was determined by hrfabms and 2D-nmr spectroscopy.