Recent Advances in Substrate-Controlled Asymmetric Induction Derived from Chiral Pool α-Amino Acids for Natural Product Synthesis

Abstract

Chiral pool α-amino acids have been used as powerful tools for the total synthesis of structurally diverse natural products. Some common naturally occurring α-amino acids are readily available in both enantiomerically pure forms. The applications of the chiral pool in asymmetric synthesis can be categorized prudently as chiral sources, devices, and inducers. This review specifically examines recent advances in substrate-controlled asymmetric reactions induced by the chirality of α-amino acid templates in natural product synthesis research and related areas.

Keywords: asymmetric induction; chiral pool; natural product; total synthesis; α-amino acid.

Figure 1

Three categories of chiral pool use in asymmetric synthesis.

Figure 2

Representative α-amino acids.

Scheme 1

Total syntheses of castanospermines 4 and 7.

Scheme 2

Total synthesis of (−)-allonorsecurinine (10).

Scheme 3

Total syntheses of ent-citrinalin B (15) and cyclopiamine B (16).

Scheme 4

Total synthesis of penibruguieramine A (22).

Scheme 5

Cu-catalyzed arylation of cyclo-(Trp-Phe) 23.

Scheme 6

Total synthesis of (+)-naseseazines A and B.

Scheme 7

Diastereoselective cyclization for pyrroloindoline skeleton.

Scheme 8

Total syntheses of (−)-brevicompanine B (38) and (+)-aszonalenin (40).

Scheme 9

Total syntheses of verruculogen (45) and fumitremorgin A (46).

Scheme 10

Total synthesis of (−)-acetylaranotin (49).

Scheme 11

Total synthesis of rigidiusculamide A (53).

Scheme 12

Total synthesis of (−)-α-kainic acid (60).

Scheme 13

Total synthesis of iso-haouamine B (64).

Scheme 14

Total synthesis of (+)-erysotramidine (70).

Scheme 15

Total syntheses of (+)-241D (74) and isosolenopsin (76).

Scheme 16

De novo synthesis of orthogonally protected legionaminic acid 80.