Asymmetric Synthesis of Isochromanone Derivatives via Trapping Carboxylic Oxonium Ylides and Aldol Cascade

An efficient asymmetric synthesis of isochromanone derivatives was realized through Z-selective-1,3-OH insertion/aldol cyclization reaction involving acyclic carboxylic oxonium ylides. The combination of achiral dirhodium salts and chiral N,N’-dioxide-metal complexes, along...

Bacterial Product Template Domain: An Evolutionary Intermediate between Dehydratase and Aldol Cyclase of Type I Polyketide Synthases

The product template (PT) domains act as an aldol cyclase to control the regiospecific aldol cyclization of the extremely reactive poly-β-ketone intermediate assembled by an iterative type I polyketide synthases (PKSs). Up to now, only the structure of fungal PksA PT that mediates the first-ring cyclization via C4-C9 aldol cyclization is available. We describe here the structural and computational characterization of a bacteria PT domain that controls C2-C7 cyclization in orsellinic acid (OSA) synthesis. Mutating the catalytic His949 of the PT abolishes production of OSA and results in a tetraacetic acid lactone (TTL) generated by spontaneous O-C cyclization of the acyl carrier protein (ACP)-bound tetraketide intermediate. Crystal structure of the bacterial PT domain closely resembles dehydrase (DH) domains of modular type I PKSs in the overall fold, dimerization interface and catalytic “His-Asp” dyad organization, but is significantly different from PTs of fungal iterative type I PKSs. QM/MM calculation reveals that the catalytic His949 abstracts a proton from C2 and transfers it to C7 carbonyl to mediate the cyclization reaction. According to the structural similarity to DHs and the functional similarity to fungal PTs, we propose that the bacterial PT represents an evolutionary intermediate between the two tailoring domains of type I PKSs.

A Regioselective [4+2] Annulation Approach to 5-Acylindolizine-7-carbonitriles: Generation of Poly-substituted Pyridines

Reaction of β-ketonitrile and N-substituted pyrrole-2-carboxaldehyde in the presence of piperidinium acetate in CH3CN permitted regioselective access to 5-acyl-6-arylindolizine-7-carbonitrile through a domino Knoevenagel condensation-intramolecular aldol cyclization sequence. A wide range...

One-pot asymmetric synthesis of a hexahydrophenanthridine scaffold containing five stereocenters via an organocatalytic quadruple-cascade reaction

An organocatalytic enantioselective aza-Michael-Michael-Michael/aldol cyclization quadruple-cascade reaction of 2-amino-β-nitrostyrenes and α,β-unsaturated aldehydes has been developed for the construction of fully substituted hexahydrophenanthridine.

Enantioselective organocatalytic vinylogous aldol−cyclization cascade reaction of 3-alkylidene oxindoles with o-quinones

Spirocyclic o-quinone analogues showed a broad spectrum of applications as biologically active compounds. We herein reported the chiral bifunctional-squaramide catalysed asymmetric vinylogous aldol−cyclization cascade reaction between 3-alkylidene oxindoles and o-quinones....

Copper-catalyzed asymmetric tandem borylative addition and aldol cyclization

A highly enantioselective asymmetric copper-catalyzed tandem conjugate addition/aldol cyclization of electron-deficient olefins with B2pin2 was developed, which provided a rapid access to indanes bearing three consecutive chiral stereogenic centers.

Catalytic enantioselective synthesis of carbocyclic and heterocyclic spiranes via a decarboxylative aldol cyclization

The synthesis of a variety of enantioenriched 1,3-diketospiranes from the corresponding racemic allyl β-ketoesters via an interrupted asymmetric allylic alkylation is disclosed.