First Total Synthesis of Cryptolaevilactones, Unique Spiromeroterpenoids

Area of Science:

• Natural Product Chemistry
• Organic Synthesis
• Medicinal Chemistry

Background:

• Cryptolaevilactones (CLs) A-L (1-12) are twelve known spiromeroterpenoids.
• These compounds possess a unique spiro[3.5]nonene skeleton derived from polyketide and monoterpene precursors.
• CLs A-C and L (1-4) are diastereomers with varying configurations at three chiral centers within the spiro moiety.

Purpose of the Study:

• To report the first total syntheses of Cryptolaevilactones A-C (1-3).
• To identify and characterize new natural products from Cryptocarya laevigata.

Main Methods:

• A convergent synthetic strategy was employed.
• The synthesis involved the construction of three key components: a styryl group, a lactone chain, and a spiro ring moiety (isopropylspiro[3.5]nonenone).

Main Results:

• The first total syntheses of compounds 1, 2, and 3 were successfully accomplished.
• A previously unreported compound, designated CL N (13), was isolated and identified from Cryptocarya laevigata.

Conclusions:

• The study demonstrates a viable synthetic route to Spiromeroterpenoids CLs A-C.
• The identification of CL N expands the known structural diversity of natural products from Cryptocarya laevigata.