Synthesis of olivetol‐4,6−¹⁴C₂, and its conversion to (–)–δ⁹‐6a, 10a‐<i>trans</i>‐tetrahydrocannabinol‐2,4−¹⁴C₂ via (–)–Δ⁸‐6a, 10a‐<i>trans</i>‐tetrahydrocannabinol‐2,4−¹⁴C₂

Abstract

Abstract Olivetol‐4,6− 14 C 2 (III) was prepared by condensing diethyl‐malonate‐2− 14 C with 3‐nonen‐2‐one followed by hydrolysis, decar‐boxylation and oxidation. Reaction with (+)‐trans‐p‐menthadien‐2,8‐ol‐l provided (–) — Δ 8 6a, 10a‐trans‐tetrahydrocannabinol‐2,4− 14 C 2 (IV) which was isomerized to (–) — Δ 9 ‐6a, 10a‐trans‐tetrahydrocannabinol‐2,4− 14 C 2 (V). On a scale of 3–5 mmole, malonate‐2− 14 C yields 45–50% of chromatographically pure olivetol‐4,6− 14 C 2 , which on a 2 mmole scale, gave a 56% radiochemical yield of purified tetrahydrocannabinols. Both the (–) — Δ 8 ‐THC‐2,4− 14 C 2 and (–) — Δ 9 ‐THC‐2,4− 14 C 2 had greater [α] D than previously reported.