The phosphate ester group in secondary metabolites.

Covering: 2000 to mid-2021The phosphate ester is a versatile, widespread functional group involved in a plethora of biological activities. Its presence in secondary metabolites, however, is relatively rare compared to other functionalities and thus is part of a rather unexplored chemical space. Herein, the chemistry of secondary metabolites containing the phosphate ester group is discussed. The text emphasizes their structural diversity, biological and pharmacological profiles, and synthetic approaches employed in the phosphorylation step during total synthesis campaigns, covering the literature from 2000 to mid-2021.

Rhodium(III)-Catalyzed Synthesis of Skipped Enynes via C(sp3 )-H Alkynylation of Terminal Alkenes.

The RhIII -catalyzed allylic C-H alkynylation of non-activated terminal alkenes leads selectively to linear 1,4-enynes at room-temperature. The catalytic system tolerates a wide range of functional groups without competing functionalization at other positions. Similarly, the vinylic C-H alkynylation of α,ß- and ß,γ- unsaturated amides gives conjugated Z-1,3-enynes and E-enediynes.

Total Synthesis and Structural Validation of Phosdiecin A via Asymmetric Alcohol-Mediated Carbonyl Reductive Coupling.

The first total synthesis and structural validation of phosdiecin A was accomplished in 13 steps through asymmetric iridium-catalyzed alcohol-mediated carbonyl reductive coupling. The present route is the shortest among >30 total and formal syntheses of fostriecin family members.

Catalytic Enantioselective Allylations of Acetylenic Aldehydes via 2-Propanol-Mediated Reductive Coupling.

Cyclometalated π-allyliridium C,O-benzoates modified by ( S)-SEGPHOS or ( S)-Cl,OMe-BIPHEP catalyze enantioselective 2-propanol-mediated reductive couplings of diverse nonmetallic allyl pronucleophiles with the acetylenic aldehyde TIPSC≡CCHO. Absolute stereochemistries of the resulting secondary homoallylic-propargylic alcohols were assigned using Rychnovsky's competing enantioselective conversion method.

Catalytic Asymmetric Synthesis and Stereochemical Revision of (+)-Cryptoconcatone H.

The total synthesis and structural revision of (+)-cryptoconcatone H are described. Guided by computational studies for the final structure assignment, the stereogenic centers at the tetrahydropyran moiety of (+)-cryptoconcatone H were assembled through catalytic asymmetric methodologies: Krische allylation, cross-metathesis reaction, and THP formation via Pd(II)-catalyzed cyclization. Finally, a Krische allylation reaction established the last stereocenter, and the lactone moiety was formed by ring-closing metathesis.