Angiogenesis is a fundamental process in reproduction and wound healing. Under these conditions, neovascularization is tightly regulated. Unregulated angiogenesis may lead to several angiogenic diseases (rheumatoid arthritis, diabetic retinopathy, juvenile hemangiomas) and is thought to be indispensable for solid tumor growth and metastasis.

The phenanthroizidines alkaloids are natural products with a pentacyclic skeleton, a phenantrene ring fused to a satured N-heterocycle generally an indolizidines or quinolizidines. This family includes close to 70 structurally related models that exhibit interesting biological properties, especially profound cytotoxic activity, and have shown to provide other medicinal benefits including mitotic, antileukemic, antibacterial and antibiotic activities. As a consequence of their promising biological profile, coupled with their low natural abundance and unusual architecture, the phenanthrolizidine alkaloids have engendered an impressive number of synthetic studies for the purpose of fundamental research and drug development.

In this STSM, I am suggesting the synthesis of Boehmeriasin A (1) and the future biological evaluation of its antiangiogenic activity. The synthesis will start from the conversion of the ethanolpiperidine 3 to the corresponding aldehyde 2 which acts as nucleophile acceptor with the appropriate Grignard reagent (Scheme 1). The synthetic   scheme   will   take   into   consideration   also   intramolecular   crotonic condensation and radical cyclization mediated by AIBN and Bu3SnH. After the completion of the batch synthesis I will try to apply the synthetic scheme using Flow Chemistry in order to avoid all the disadvantages of the batch synthesis.

Furthermore,  I will  have the possibility to learn  the use of the particular instrument  which  is  used  in  Flow  Chemistry  and  can  be  provided  by  Professor ………………….at  the  University  of  ………………and  also  to  learn  the  new technology of Flow Chemistry.



 Scheme 1. Retrosynthetic analysis of Boehmeriasin A (1).