17581-86-1

Multicomponent reactions that involve interception of onium ylides through Aldol, Mannich, and Michael addition with corresponding bench-stable acceptors have demonstrated broad applications in synthetic chemistry. However, because of the high reactivity and transient survival of these in situ generated intermediates, the substitution-type interception process, especially the asymmetric catalytic version, remains hitherto unknown. Herein, a three-component asymmetric allylation of α-diazo carbonyl compounds with alcohols and allyl carbonates is disclosed by employing a ternary cooperative catalysis of achiral Pd-complex, Rh2(OAc)4, and chiral phosphoric acid CPA. This method represents the first example of three-component asymmetric allylic alkylation through an SN1-type trapping process, which involves a convergent assembly of two active intermediates, Pd-allyl species, and enol derived from onium ylides, providing an expeditious access to chiral α,α-disubstituted ketones in good to high yields with high to excellent enantioselectivity. Combined experimental and computational studies have shed light on the mechanism of this novel three-component reaction, including the critical role of Xantphos ligand and the origin of enantioselectivity.

We have developed robust in vivo and in vitro biocatalytic systems that enable reduction of α,β-unsaturated carboxylic acids to allylic alcohols and their saturated analogues. These compounds are prevalent scaffolds in many industrial chemicals and pharmaceuticals. A substrate profiling study of a carboxylic acid reductase (CAR) investigating unexplored substrate space, such as benzo-fused (hetero)aromatic carboxylic acids and α,β-unsaturated carboxylic acids, revealed broad substrate tolerance and provided information on the reactivity patterns of these substrates. E. coli cells expressing a heterologous CAR were employed as a multi-step hydrogenation catalyst to convert a variety of α,β-unsaturated carboxylic acids to the corresponding saturated primary alcohols, affording up to >99percent conversion. This was supported by the broad substrate scope of E. coli endogenous alcohol dehydrogenase (ADH), as well as the unexpected CC bond reducing activity of E. coli cells. In addition, a broad range of benzofused (hetero)aromatic carboxylic acids were converted to the corresponding primary alcohols by the recombinant E. coli cells. An alternative one-pot in vitro two-enzyme system, consisting of CAR and glucose dehydrogenase (GDH), demonstrates promiscuous carbonyl reductase activity of GDH towards a wide range of unsaturated aldehydes. Hence, coupling CAR with a GDH-driven NADP(H) recycling system provides access to a variety of (hetero)aromatic primary alcohols and allylic alcohols from the parent carboxylates, in up to >99percent conversion. To demonstrate the applicability of these systems in preparative synthesis, we performed 100 mg scale biotransformations for the preparation of indole-3-aldehyde and 3-(naphthalen-1-yl)propan-1-ol using the whole-cell system, and cinnamyl alcohol using the in vitro system, affording up to 85percent isolated yield.

We report a stereoselective and site-specific allylic alkylation of Schiff base activated amino acids and small peptides via a Pd/Cu dual catalysis. A range of noncoded α,α-dialkyl α-amino acids were easily synthesized in high yields and with excellent enantioselectivities (up to >99% ee). Furthermore, a direct and highly stereoselective synthesis of small peptides with enantiopure α-alkyl or α,α-dialkyl α-amino acids residues incorporated at specific sites was accomplished using this dual catalyst system.

A simple and efficient method for the synthesis of primary allylic alcohols from monosubstituted epoxy acetates has been developed using titanocene(III) chloride mediated epoxide ring opening via acetate elimination.

In this research, three categories of phenylpropanoid glycosides (PPGs) were designed and synthesized with PPGs isolated from Rhodiola rosea L. as lead compounds. Their inhibitory abilities toward acetylcholinesterase (AChE) and xanthine oxidase (XOD) were also tested. Some of the synthetic PPGs exhibited excellent enzyme inhibitory abilities.

The synthesis of several 1,2,5-oxadiazole-2-oxide (Furoxan) analogues is described herein. These compounds were prepared in an effort to probe the SAR around the phenyl substituent and oxadiazole core for our studies toward thioredoxin-glutathione reductase (TGR) inhibition and antischistosomal activity.