Xiaochuan Chen

Catalytic Ugi-Type Condensation of α-Isocyanoacetamide and Chiral Cyclic Imine: Access to Asymmetric Construction of Several Heterocycles

Several novel heterocycles have been constructed asymmetrically on the basis of a catalytic Ugi-type condensation of α-isocyanoacetamide and chiral cyclic imine. The combination of phenylphosphilic acid and trifluoroethanol is exploited to promote an Ugi-type reaction with α-isocyanoacetamide for the first time. By means of this reaction, chiral 3-oxazolyl morpholin-2-one/piperazin-2-one derivatives are synthesized with high yields and excellent stereoselectivities. As electron-rich azadienes, these condensation products are further transformed to fused tricyclic frameworks by treatment with appropriate dienophiles such as maleic anhydride and unsaturated acyl chlorides via domino processes. Moreover, a one-pot, three-component synthesis of the chiral tricyclic frameworks from isocyanoacetamide, imine, and maleic anhydride is also feasible.

An Asymmetric Ugi Three-Component Reaction Induced by Chiral Cyclic Imines: Synthesis of Morpholin– or Piperazine–Keto-carboxamide Derivatives

A series of chiral 5,6-dihydro-1,4-oxazin-2-one substrates, as preformed cyclic aldimines and ketoimines, were employed to develop a new asymmetric Ugi three-component reaction for the first time. The Ugi reaction of the imines, isocyanides, and carboxylic acids opens an efficient access to novel morpholin-2-one-3-carboxamide compounds. The chiral imines showed promising stereoinduction for the new chiral center of the Ugi products, and predominant trans-isomers were obtained in the most cases. Addition of some Lewis acids or proton acids could improve the diastereoselectivity further but usually led to a drop in total yield. The Ugi-3CR could be extended to the stereoselective synthesis of ketopiperazine-2-carboxamide derivatives.

Asymmetric total synthesis of (-)-jorunnamycins A and C and (-)-jorumycin from L-tyrosine.

Three renieramycin-type antitumor alkaloids, (-)-jorunnamycins A (1) and C (2) and (-)-jorumycin (3), have been synthesized by a new convergent approach, which features a highly regio- and stereoselective Pictet-Spengler cyclization to couple the isoquinoline and the trisubstituted phenylalaninol partners. This synthetic strategy opens an economical access to these important antitumor alkaloids with high yields: (-)-jorunnamycin A, as a common precursor to other renieramycin-type alkaloids and their analogues, is obtained with 18.1% overall yield from l-tyrosine.

Stereoselective Synthesis of (+)-Annuionone A and (-)-Annuionone B

A stereoselective synthetic approach was utilized to synthesize enantiopure annuionones A (1b) and B (2b), two ionone-type norsesquiterpenoids that both bear a 6-oxabicyclo[3.2.1]octane framework and possess allelopathic activity. A stereoselective Diels-Alder reaction based on chiral trisubstituted dienophile 20 was employed to obtain the optically active polysubstituted cyclohexane core of both natural products. Using this approach, (+)-annuionone A (1b) and (-)-annuionone B (2b) were synthesized from lactol (+)-15 in 10% overall yield.

A Stereoselective Approach toward (−)-Lepadins A–C

A new short approach to (-)-lepadins A-C has been developed based on a stereocontrolled Diels-Alder reaction employing a chiral dienophile. With this approach, (-)-lepadin B is synthesized from 5-deoxy-d-ribose in 13 steps with 14.8% overall yield. The cis-decahydroquinoline core containing five stereocenters could be rapidly constructed via stereoselective cycloaddition and subsequent five-step one-pot hydrogenation-cyclization.

A Flexible and Divergent Strategy to Flavonoids with a Chiral A-Ring Featuring Intramolecular Michael Addition: Stereoselective Synthesis of (+)-Cryptocaryone, (+)-Cryptogione F, and (+)-Cryptocaryanones A and B, as Well as (+)-Cryptochinones A and C

A flexible strategy has been developed to synthesize divergent flavonoids bearing a chiral A-ring. As two key steps, the coupling via a boron-mediated aldol condensation and the cyclization via a highly stereoselective intramolecular Michael addition of 1,3-diketone proceed under mild conditions; thus, the chiral flavonoids bearing C-7 oxy functional groups or olefinic bonds are both easily accessible. Using this approach, the first synthesis of (+)-cryptogione F, (+)-cryptocaryanone B, and (+)-cryptochinones A and C, as well as stereoselective synthesis of (+)-cryptocaryone and (+)-cryptocaryanone A, were achieved from 2-deoxy-d-ribose in high overall yields.