Academic literature on the topic 'Palmerolide C'

Herein, we describe the stereoselective synthesis of highly functionalized advanced key intermediates towards the total synthesis of the revised structure of palmerolide C and 10-epi-palmerolide C in a convergent manner.

The palmerolides are an emerging class of polyketide natural products isolated from marine organisms inhabiting the Antarctic Sea. Although there has been a substantial effort to prepare the most active family member palmerolide A, no synthetic work has been performed in the area of the other members of the family; palmerolides B and C of different ring structure. These compounds are particularly interesting due to their complex structures with undefined stereochemistry and both display high selectivity towards human melanoma cancer cell lines. A highly convergent strategy to access palmerolide C has been developed, relying on the assembly of three fragments using key bond couplings at C6-C7 (boron-mediated aldol reaction/dehydration) and C14-C15 (Julia-Kocienski olefination), followed by a suitable macrolactonisation step and Buchwald enamide formation. Prior to subunit synthesis, the relative configuration of the C8-C10 stereotriad was resolved via the synthesis of diastereomeric degradation fragments by the application of organocatalytic cross aldol reactions and a suitable 1,3-selective reduction.

First chapter of the thesis describes the total synthesis of tetrahydropyran containing natural products, diospongin A, cryptopyranmoscatone B2, hydroxy δ-lactone containing natural product cryptofolione and macrolactone Sch 725674. Section A of this chapter deals with total synthesis of diospongin A 1, involving a vinylogous Mukaiyama aldol reaction of the silyl enol ether 2 with the aldehyde 3. The natural product was synthesized in 5 linear steps from benzaldehyde with 13.2% overall yield (Scheme 1). Scheme 1: Total synthesis of diospongin A 1. Section B of this chapter, describes the total synthesis of cryptofolione 7, a δ-lactone containing a dihydroxy unit in the side chain. Enzymatic resolution of a β-hydroxy ketone 4 was utilized for the synthesis of aldehyde 6, which was further elaborated to access cryptofolione 7. The key reactions in the synthesis include base catalyzed isomerisation of aldehyde with DBU, Brown’s allylation and ring closing metathesis reaction (Scheme 2). Scheme 2: Total synthesis of cryptofolione 7. Section C of chapter 1 discloses the total synthesis of cryptopyaranmoscatone B2 (11), a natural product possessing a tetrahydropyran and δ-lactone units. Iron (III) chloride catalyzed cyclization of the diol 9 derived from commercially available lactol 8 furnished the tetrahydropyran is the key reaction in the synthesis (Scheme 3). Scheme 3: Stereoselective total synthesis of cryptopyranomoscatone B2 (11). . Section D of chapter 1 deals with the total synthesis of (+)-Sch 725674 (16) starting from known lactol 12 derived from 2-deoxy ribose. Addition of 4-pentenylmagnesium bromide to lactol 12 provided the diol 13. Elaboration of 13 with the acetate 14 by olefin cross metathesis and further transformations led to Sch 725674 (16) (Scheme 4). Scheme 4: Total synthesis of (+)-Sch 725674 (16). Chapter 2 of the thesis is concerned with the efforts towards the total synthesis of palmerolide C. During the course of present investigation, the putative structure of palmerolide C was revised. The efforts concerning the synthesis of putative and revised structures of palmerolide C 18 and 20 from tartaric acid and D-ribose is described (Scheme 5). Scheme 5: Towards the total synthesis of the proposed and revised structure of palmerolide C.