The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

Abstract

The desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds is a powerful tool for the construction of ring systems bearing multiple stereocenters including all-carbon quaternary stereocenters, which are widely useful chiral building blocks for the total synthesis of structurally complex natural products. On the other hand, terpenoids and alkaloids, with their intricate and diverse skeletal frameworks as well as the broad range of biological activities, have long been a major focus for synthetic chemists. Over the past fifteen years, significant progress has been made in the total synthesis of complex terpenoid and alkaloid natural products by strategically applying desymmetric enantioselective reduction. Advance before 2016 in this area has been overviewed in an elegant review article. Since then, a series of more challenging terpenoid and alkaloid natural products have been synthesized utilizing a desymmetric enantioselective reduction strategy of cyclic 1,3-dicarbonyl compounds as a key transformation. This review will summarize the application of this strategy in the total synthesis of terpenoid and alkaloid natural products from the year 2016 to 2025. We first focus on the synthesis of several terpenoids and alkaloids through the desymmetric enantioselective reduction of five-membered cyclic 1,3-dicarbonyl compounds. Subsequently, the utilization of six-membered cyclic 1,3-dicarbonyl compounds for the synthesis of some terpenoids natural products is described.

Keywords: alkaloids; cyclic 1,3-dicarbonyl compounds; desymmetrization; enantioselective reduction; terpenoids.

Figure 1

Several representative terpenoid and alkaloid natural products synthesized by applying desymmetric enantioselective reduction strategy of cyclic 1,3-dicarbonyl compounds before 2016.

Figure 2

Selected terpenoid and alkaloid natural products synthesized by applying desymmetric enantioselective reduction strategy of cyclic 1,3-dicarbonyl compounds in 2016–2025.

Scheme 1

The total synthesis of (+)-aplysiasecosterol A (6) by Li [14].

Scheme 2

The total synthesis of (−)-cyrneine A by Han [31].

Scheme 3

The total syntheses of three cyrneine diterpenoids by Han [–32].

Scheme 4

The total synthesis of (−)-hamigeran B and (−)-4-bromohamigeran B by Han [51].

Scheme 5

The total synthesis of (+)-randainin D by Baudoin [53].

Scheme 6

The total synthesis of (−)-hunterine A and (−)-aspidospermidine by Stoltz [58].

Scheme 7

The total synthesis of (+)-toxicodenane A by Han [–66].

Scheme 8

The formal total synthesis of (−)-conidiogeone B and total synthesis of (−)-conidiogeone F by Lee and Han [72].

Scheme 9

The total syntheses of four conidiogenones natural products by Lee and Han [72].

Scheme 10

The total synthesis of (−)-platensilin by Lou and Xu [82].

Scheme 11

The total synthesis of (−)-platencin and (−)-platensimycin by Lou and Xu [82].

Scheme 12

The total synthesis of (+)-isochamaecydin and (+)-chamaecydin by Han [86].