Total Synthesis of Varitriol, Varioxirane, and Enantiomer of the Proposed Biosynthetic Precursor

Abstract

The first stereoselective total synthesis of varioxirane was accomplished, and the proposed biosynthetic pathway was supported by converting varioxirane to (+)-varitriol. The first total synthesis of enantiomer of the proposed biosynthetic precursor, (1E,3S,4R,5E)-1-(2-(hydroxymethyl)-3-methoxyphenyl)hepta-1,5-diene-3,4-diol, was also achieved by utilizing the unreacted allylic alcohol obtained during the Sharpless kinetic resolution step. Other key steps include the Horner-Wadsworth-Emmons reaction and the diastereoselective reduction of α,β-unsaturated ketone to its corresponding alcohol.

Varioxiranols A–G and 19-O-Methyl-22-methoxypre-shamixanthone, PKS and Hybrid PKS-Derived Metabolites from a Sponge-Associated Emericella variecolor Fungus

“…The relative configuration of C-10 and C-11 was determined by the 3 J H,H value in association with the NOE interactions. , The 3 J H‑10/H‑11 value (4.0 Hz) was indicative of a gauche relationship of H-10 and H-11. The NOE interactions between H-9/H-12, H-10/H-12, and H-9/OH-11 (Figure ) in association with the absence of an NOE interaction between H-10/OH-11 and OH-10/H-12 suggested the relative configuration at the side chain of 1 to be 10 R* and 11 S* , which were the same as those of the known analogue (1 E ,5 E )-1-(2-(hydroxymethyl)-3-methoxyphenyl)­hepta-1,5-diene-3,4-diol ( 9 ) . The absolute configuration of 1 was determined on the basis of the modified Mosher’s method used for the determination of the configuration of the acyclic 1,2-diol .…”

“…Diagnostic Δδ RS (δ (R) ‑MPA ester – δ (S) ‑MPA ester ) data (Figure ) resulted in positive Δδ RS values for H-9 and H-10, whereas H-11 and H-12 showed negative Δδ RS values. These data were in accordance with 10 R and 11 S configurations, which were the same as those of 9 , whose enantiomer was previously obtained using total synthesis …”

“…Compounds 10 and 11 were identical to varitriol , and varioxirane, respectively, according to the spectroscopic comparison. Analyses of 1D and 2D NMR spectroscopic data identified 12 as pre-shamixanthone, a product from A. nidulans when its cryptic PKS genes were activated . In addition, five xanthone analogues were identical to tajixanthone ( 13 ), tajixanthone methanoate ( 14 ), tajixanthone hydrate ( 15 ), 15-acetyltajixanthone hydrate, and shamixanthone …”

A dual role for acetohydrazide in Pd-catalyzed controlled C(sp3)–H acetoxylation of aldehydes

“…Herein, we describe a novel palladium catalyzed TDG approach for the direct and selective C(sp 3 )-H acetoxylation of aldehydes. This developed methodology provides a catalysis route for C-O bond formation in a straightforward fashion, which successfully suppresses the undesired oxidation of the -CHO group and the acetoxylation products could be transformed into various biologically active compounds such as indeno[1,2-b]quinolines, 21 ve-membered azacyclic compounds, 22 mycophenolic acid which is an important antiparasitic, antineoplastic and antiviral agent, an intermediate of coleophomone which has antifungal activity and shows inhibition of human heart chymase, 24 varitriol which is associated with high levels of biological activity toward renal, CNS, and breast cancer cell lines 25 and an s-trans-heterodiene framework 26 (see Scheme 2). Therefore, the methodology of aldehyde-directed selective acetoxylation of C(sp 3 )-H bonds can greatly reduce the steps of the total synthesis of these biologically active compounds.…”

Visible-Light-Induced Pd-Catalyzed Radical Strategy for Constructing C-Vinyl Glycosides

“…Although synthetic routes for C -aryl glycosides have been widely explored, the C -glycosyl styrenes, which are versatile starting compounds for, e.g., varitriol, C -glycosyl aldehydes, UDP sugar derivatives, pyranopyran carbohydrate amino acids, and some natural products, remain challenging. At the outset, an intramolecular radical cyclization strategy was applied to prepare C -glycopyranosyl styrenes.…”