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Identifier

000280288

Title

Βιομιμητική Σύνθεση των Litseaverticillols B, E, I και J και Επαναπροσδιορισμός της Δομής της Litseaverticillol E

Alternative Title

Biomimetic Total Synthesis of Litseaverticillols B, E, I and J and Structural Reassignment of Litseaverticillol E

Author

Μαργαρός, Γιάννης

Thesis advisor

Βασιλικογιαννάκης, Γεώργιος

Abstract

In 2001 the first of a series of papers was published disclosing the isolation of a family of novel sesquiterpenes, the litseaverticillol alongside studies into their biological activity. These natural products exhibited potent and selective anti-HIV activity, inhibiting HIV-1 replication in HOG.R5 cells with IC50 values ranging between 2 and 15 μM. We set forth on a program directed towards the total synthesis of these sesquiterpenes inspired by their unique skeleton and their biological activity. Based upon our hypothesis relating to their biogenetic origins, the total synthesis of Litseaverticillols Α, C, D, F, G was concluded in 2003, followed by total synthesis of Litseaverticillols Β, Ε, I, J in 2004, the latter resulting in the structural reassignment of Litseaverticillol E. The highlight of the syntheses is an elegant and highly efficient one-pot, 5-synthetic cascade operation, initiated by the [4 + 2] cycloaddition of singlet oxygen (1Ο2) to furan 11b first affording the fleeting hydroperoxide adduct Ib, which is then opened nucleophilically (ΜeΟΗ) to yield quantitatively and exclusively hydroperoxide 90b. Reduction of latter using (CH3)2S yields a mixture of unstable diastereomeric hemiacetals 91b. Base mediated collapse of the hemiacetals 91b followed by elimination of MeOH furnishes the key intermediate in the proposed biosynthesis, (Ζ)-1,4-enedione 12b. In situ intramolecular aldol reaction of 12b induced by (i-Pr)2NEt, furnishes Litseaverticillol B (2). Further regioselective oxidation of Litseaverticillol B, affords all the three possible products that could be derived by an ene-reaction between 1Ο2 and the Δ10,11 double bond of the side chain, which are Litseaverticillols I, J (9, 10) and the tertiary alcohol 5, whose structure matched that initially proposed for Litseaverticillol E.

Language

Greek

Subject

Biomimetic synthesis

Ene reaction

Furans photoxidation

Natural products

Singlet oxygen

Total synthesis

Αντίδραση ενίου

Βιομιμητική σύνθεση

Ολική σύνθεση