Chapter 1. Biomimetic Total Synthesis of ent-Durgamone, ent-Nakorone and ent-Abudinol B Chapter 2. Biomimetic Synthesis of Fused Polypyrans Open Access

Tong, Rongbiao (2008)

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Chapter 1. Biomimetic Total Synthesis of ent-Durgamone, ent-Nakorone and ent-Abudinol B The first biomimetic total syntheses of ent-nakorone (7 steps in 32.1% yield from farnesol), ent-durgamone (8 steps in 21% yield from geranylacetone), and ent- abudinol B (5 steps in 15.92% yield from advanced intermediates of ent- nakorone and ent-durgamone) were accomplished by combining features of tandem polyepoxide cyclization with biomimetic polyene cyclization. The present biomimetic synthesis route offers efficient access to these marine natural products. In addition, the synthesis of the tetrasubstituted alkene of ent-abudinol B demonstrates the application of pal adium-catalyzed cross-coupling of two different polycyclic ketones via the corresponding vinyl triflates, fol owed by partial hydrogenation of the resulting conjugated diene. The second generation of biomimetic total synthesis of the enantiomer of abudinol B was achieved in 8 steps from commercial y available trans-trans- farnesylacetate with 0.18% overal yield, fol owing a synthetic strategy inspired by and closely mimicking the proposed biosynthetic pathway. This synthesis demonstrates the viability of tandem oxa- and carbacyclizations of structural y complex polyepoxide-alkene substrates. This second generation synthesis features a two-directional biomimetic cyclization strategy, in which the separate polycyclic ring systems are constructed by Lewis acid-promoted tandem oxa- and carbacyclizations from a structural analog of squalene diepoxide. This demonstration of tandem cyclizations provides experimental support for the chemical viability of a proposed biogenetic pathway.

Chapter 2. Biomimetic Synthesis of Fused Polypyrans The biomimetic synthesis of fused bispyran via Lewis acid-mediated tandem oxacyclization of 1,4,7-polyepoxide is explored. Fragmentation was the main competing process for oxacyclization of skipped polyepoxides. The nature of the Lewis acid promoter is critical for the endo-regioselectivity of epoxide cyclization, although anomalous apparent retention of stereochemistry is observed at some reactive centers. The mechanistic interpretation leads us to hypothesize that the energy of the reaction transition state required for synchronous cyclizations to form polypyrans is much higher than that in the analogous synthesis of polyoxepanes, and thus the stepwise mechanism may operate.

Table of Contents

Chapter 1. Biomimetic Total Synthesis of ent-Durgamone, ent-Nakorone
and ent-Abudinol B
1.1. Introduction and Background
1.1.1. Total synthesis and biomimetic synthesis
1.1.2. Biomimetic total Synthesis of isoprenoid natural products
from squalene-like substrates Biogenesis of isoprenoid natural products Stereochemistry issues in biogenesis of isoprenoid
natural product Biomimetic synthesis of isoprenoid natural products
1.1.3. Biomimetic synthesis of polycyclic ethers Biogenesis of polycyclic ether natural products Biomimetic synthesis of polycyclic ethers Biomimetic synthesis of polycyclic ether natural products

1.1.4. Biogenesis of abudinol B and related natural products
1.1.5. Retrosynthetic analysis of abudinol B, durgamone and nakorone
1.2. Results and discussion
1.2.1. Total synthesis of ent-durgamone and bicyclic ketone
1.2.2. Total synthesis of ent-nakorone (ent-67)
1.2.3. Total synthesis of enantiomer of abudinol B (ent-64)
1.3. Biomimetic total synthesis of abudinol B from squalene-like precursor

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