BioCentury
ARTICLE | Distillery Techniques

Chemistry

October 17, 2017 4:54 PM UTC

A simplified multi-step method could enable scalable synthesis of the PKC modulator bryostatin-1 and its analogs to treat neurological diseases, HIV/AIDS and cancer. The method involved the total synthesis of bryostatin-1 or its analogs in a scalable, 29-step chemical reaction, compared with 57 steps in conventional synthesis methods. The method produced an 80% average yield per step, and final yields of over two grams. In vitro, two previously unreported bryostatin-1 analogs derived from intermediates in the 29-step reaction bound PKC β (PRKCB) with Ki values of 3.9 and 12 nM and PKC δ (PRKCD) with Ki values of 0.76 and 1.4 nM. Next steps include using the method to synthesize additional undisclosed bryostatin-1 analogs.

Neurotrope Inc. has bryostatin-1 in Phase II testing to treat Alzheimer’s disease and in preclinical testing to treat Niemann-Pick disease type C (NPC). Neurotrope and Blanchette Rockefeller Neurosciences Institute have the compound in preclinical testing to treat fragile X syndrome. ...