Novel Variant of the Tricyclooctanone Approach to Cyclopentanoid Natural Products. Synthesis of (±)‐Coriolin. Preliminary Communication

Abstract

SummaryA total synthesis of the antitumor sesquiterpene coriolin (9; racemic) in 11 steps from 3,3,6-trimethylbicyclo[2.2.2]oct-7-ene-2,.5-dione (2a/2b) is described (yield 2a/ 2b-t8: 28 "/o). The sequence is unprecedentedly short and avoids difficult separation problems. The key step in the scheme is a novel facet of oxadi-n-methane photochemistry, i.e., the steering by subtle steric effects of the P,y-unsaturated E-diketone to undergo a regioselective photorearrangement involving one P,y -enone partial chromophore. Furthermore, the overall phototransformation, which can be carried out at unusually high concentrations ( > 20% solutions), involves also a Norrish type 1 process equilibrating the two epimeric starting enediones 2a and 2b in favour of the desired stereoisomer.The antitumor sesquiterpene coriolin, (-)-(9)'), has become a testing case for the design of syntheses of medium-sized natural products of complex structures, and notably for the development of new methodologies aiming at cyclopentanoid annulation procedures [4]. We have previously demonstrated that the use of the optically active forms of tricyc1o[3.3.0.0*~*]octan-3-one provides for a versatile synthetic approach to cyclopentanoid natural products [3] [5] [6], including one towards the total synthesis of coriolin, (-)-(9) [6]. Scheme 1 summarizes an alternative to this concept which is characterized by an unprecedentedly short route to the intermediate 8 in common with previous total syntheses of (f)-coriolin (9) [2]. The key step in this scheme is a novel facet of oxadi-n-methane photochemistry, i e . , the steering by subtle steric effects of a P,y -unsaturated E -diketone to undergo a regioselective photorearrangement involving one P,y-enone partial chromophore.') Synthetic work directed towards ( * )-9, see [I]; synthesis of 8 and its conversion into (%)-9, see [4. For the isolation of (-)-9 and its biological importance, see Footnote 82 in [3].

Photochemical Approaches to Complex Chemotypes: Applications in Natural Product Synthesis

“…A similar approach by Liao and co-workers was also applied in the synthesis of (±)-Δ 9(12) -capnellene ( 525 ), which was accessed in nine steps with 20% overall yield from 2-methoxy-4-methylphenol ( 524 ) (Scheme ). Additional examples of linear triquinanes that have been assembled utilizing the oxa-di-π-methane rearrangement are (−)-complicatic acid ( 526 ), , (−)-coriolin ( 527 ), − (−)-hirsutene ( 222 ), − (+)-hirsutic acid ( 528 ), ,,, and (−)-phellodonic acid ( 529 ) (Figure ). …”

A Facile Diels−Alder Reaction with Benzene: Synthesis of the Bicyclo[2.2.2]octene Skeleton Promoted by Rhenium

“…Analysis of the spectral data along with a comparison of related compounds found in the literature led us to the assigned regioselectivity of the oxygen insertion . Oxobicyclooctenes similar to 4 have been shown to be useful precursors to cyclopentanoid terpenes and prostacyclin analogues . By comparison, reaction of phenol and N -phenylmaleimide at 170 °C for 3 days gives 36% of the enone cycloadduct as a 4:1 mixture of diastereomers .…”