Cephanolides A–J, Cephalotane-Type Diterpenoids from Cephalotaxus sinensis

Abstract

Ten new cephalotane-type diterpenoids, cephanolides A-J (1-10), and two known analogues were isolated and characterized from Cephalotaxus sinensis. Compounds 1-3 represent the first examples of A-ring-contracted cephalotane-type dinorditerpenoids, and compound 4 is an A-ring-contracted norditerpenoid. The biosynthetic pathways for compounds 1-4 are postulated with the coexisting cephalotane-type troponoids as the precursors. Compounds 11 and 12 showed significant cytotoxicities against a panel of tumor cell lines (A549, KB, HL-60, and HT-29) with IC values ranging from 0.464 to 6.093 μM.

Asymmetric Total Synthesis of Cephanolide A

“…The structure of cephanolide A ( 8 ) was also confirmed by its X‐ray crystallographic analysis. The spectroscopic data ( 1 H and 13 C NMR spectra, as well as HRMS, and CD spectra), crystal structure, and melting point of synthetic sample were fully consistent with the corresponding data for the natural product reported by Yue [4a] …”

Evolution of Strategies in Protecting‐Group‐Free Synthesis of Natural Products: A Recent Update

“…Yue and co‐workers isolated cephanolides A‐D, which are complex norditerpenoids with a tetracyclic carbon skeleton from Cephalotaxus sinensis . [ 68 ] Zhao and co‐workers [ 69 ] reported the first synthesis of (±)‐cephanolides B ( 189a ) and C ( 189b ) by tactically using a Pd‐catalyzed cascade cyclization to furnish the 6–5–6 cis‐fused tricyclic scaffold (Scheme 21). The synthesis began with Negishi coupling of commercially available 181 with alkylzinc bromide 182 followed by iodination to deliver ester 183 .…”

Asymmetric Total Synthesis of (+)‐Mannolide C

“…Cephalotaxus diterpenoids, consisting of a big family of structurally diverse natural products with a variety of biological properties, particularly antitumor activities, have been used as a fruitful source for drug discovery. [1] These natural products include cephalotane-type C 20 diterpenoids, [2] cephalotaxus C 19 troponoids, [3] other cephalotane-type C 19 norditerpenoids, [3f, 4] and A-ring-contracted cephalotane-type C 18 dinorditerpenoids, [5] only some of which have been synthesized in chemical laboratories so far. In 2016, mannolides A-C (1-3, Figure 1), three new structurally unique cephalotane-type C 20 diterpenoids, were isolated from Cephalotaxus mannii Hook f. by Yue and co-workers, [2] which were believed to be the real biosynthetic precursors of the antitumor cephalotaxus troponoids.…”

“…[2] The peculiar structural features and significant biological activities of cephalotaxus diterpenoids have aroused broad interest from the synthetic community. [7] In 1998, Mander and co-workers reported the formal synthesis of (AE)-harringtonolide (5), featuring an intramolecular arene cyclopropanation followed by a ring-expansion strategy. [8] In 2013, Tang and co-workers acomplished the total synthesis of (AE)hainanolidol and (AE)-harringtonolide (5) via an oxidopyrylium-based [5+2] cycloaddition as the key step.…”