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Bryostatin synthesis

Studies Directed Towards the Synthesis of Bryostatin

Seema Aravind, Narayana Reddy

Abstract


Thesis is structured in two different parts. The first part deals with the convergent and stereo selective synthesis of the C1-C10 fragment 3 of cytostatic macrolide bryostatin. Two of the three chiral centers were established via Sharpless Kinetic resolution on racemic allylic alcohol 10 followed by reduction with Red-Al. Diastereoselective transformation of the aldehyde 18 moiety to β-hydroxy ester 20 via an Aldol reaction, which is transformed to pyran ring 3 via chemical transformations are the key steps. The second part discuss the stereo-controlled asymmetric synthesis of C7-C16 fragment 4  of bryostatin. The key steps involved in this synthesis are the Jacobsen’s hydrolytic kinetic resolution and Reformatsky reaction to build the C11-C16 fragment. The vinyl Grignard has been used to construct the C7-C10 fragment. Cross-metathesis was successfully used to couple both the fragments, C7-C10 and C11-C16 to produce a key component 46. Oxa-Michael reaction has been employedto construct the pyran ring system 4.


Keywords


Bryostatin; Antineoplastic activitity; Aldol reaction; Lactonization; Jacobsen’s kinetic resolution; Reformatsky reaction; Cross-metathesis

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References and notes

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