Leland Stanford Junior University

Jack Leider Sloane

Paul A Wender

Stephen Ho

Ryan Quiroz

Matthew S Jeffreys

Clayton Hardman

Matthew C Stevens

Akira Shimizu

Steven Ryckbosch

Xiaoyu Zang

Katherine N Keenan

Nancy Lynn Benner

Methods for preparing a variety of bryostatin compounds are provided. The subject methods provide for preparation of bryostatin 1 in multi-gram quantities in a low and unprecedented number of convergent synthetic steps from commercially available materials. The subject methods are scalable with low estimated material costs and can provide enough material to meet clinical needs. Also provided are a variety of bryostatin analog compounds, and prodrug forms thereof, which are synthetically accessible via the subject methods and pharmaceutical compositions including the same.

Bryostatin compounds and methods of preparing the same

Embodiments of prodrugs of PKC modulators that show efficacy coupled with low levels of toxicity and improved stability are provided. The prodrug compounds are useful in academic research (animal studies), as candidates for preclinical research, and as therapeutic agents. By taking advantage of a pharmacophore-based strategy, this design strategy provides access to prodrugs of PKC modulators of diverse scaffolds including tigliane diterpenes, ingenane diterpenes, daphnane diterpene orthoesters, diacylglycerols, and bryostatins, and analogs thereof. In particular, embodiments of the prodrug ingenane esters having substitutions at C20 and their use as therapeutic agents are provided.

Prodrug derivatives of protein kinase C modulators

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Stanford, CA, United States of America

Jack Leider Sloane