Stereoselective synthesis of (–)-acorenone and (–)-acorenone B; the absolute configuration of natural (–)-acorenone

Abstract

Su.tnmai/y The spiroenone (7), stereoselectively prepared from (+)-p-menth-l-ene (3) in four steps, was converted by two different reaction sequences into the natural sesquiterpenes (-)-acorenone ( 1) and (-)-acorenone B (2), respectively, thus establishing the absolute configuration of (1).MUCH attention has been directed recently towards the development of new syntheses of the acoranes, a group of sesquiterpenes with a spiro [4.5]decane skeleton. We describe here a new route to (-)-acorenonel(1) and to (-)-acorenone B 2 p 3 (2), two members of the acorane family.Ozonolysis of ( +)-p-menth-l-ene4 (3) ( [ a ] g + log", G 1.1, CHC1,) in methanol, followed by reductive cleavage, gave a ketoaldehyde, which was cyclised5 (piperidine, AcOH, CHCl, reflux) to the ap-unsaturated aldehyde (4) (60% overall yield). The C=C double bond of (4) was hydrogenated (Pd-CaCO,, K,CO,, MeOH, H,O), as expected, on the side of the cyclopentane ring opposite to the isopropyl group ; after spontaneous epimerization, the trans,transcyclopentane derivative (5) was obtained 95% pure t(80y0 yield). The structure of (5) was confirmed by its identity with the hydrogenation product (PtO,, AcOEt) of trans,-

Spirodionic Acid, a Novel Metabolite from Streptomyces sp., Part 2: Total Synthesis through a Twofold Michael Addition as a Selective Spiroannelation Strategy

“…Thus, in comparable reactions, a vicinal methyl substituent on a five‐ or six‐membered ring induced a selectivity of 80:206g or 90:10,7a respectively, whereas the bulky isopropyl substituent on a five‐membered ring led to selectivities exceeding 92:8 6g. 7b,c…”

“…The spiroannelation of cyclohexenone rings by using a Michael addition and subsequent aldol reaction (pathway A) has been achieved with both plain cycloalkanecarbaldehydes7c that is, compounds without a carbonyl moiety adjacent to the future spiro carbon, and 2‐formylcycloalkanones 13. The second carbonyl moiety in the latter compounds in principle facilitates the 1,4‐addition, yet, at the same time it eases the deformylation, thus leading to undesirable reaction modes.…”

Total syntheses of natural products containing spirocarbocycles

“…Pesaro et al used a Robinson annulation in 1978 to synthesise both (−)-acorenone and (−)-acorenone B, in 4 steps starting from (+)-p-menth-1-ene 74 (Scheme 19).…”

Microbial Terpenes: A Perspective on Their Chemistry and Biosynthesis

“…For this purpose, the absolute configuration of natural 21 had to be established. Although several enantioselective routes were already known, [41][42][43] we felt that it would be more interesting to develop a new synthetic method rather than just repeating a known route to obtain the required reference compound. Trichoderma fungi are widespread plant-growth-promoting symbionts 44 that live in soil, root, and foliar ecosystems.…”

“…The unambiguously established absolute configuration of tricho-acorenol (21) in T. harzianum permitted further interesting studies on the biosynthetic pathway towards this spirocyclic sesquiterpene, including its stereochemical details. For an in-depth evaluation of the biosynthesis, a robust route for the synthesis of deuterated isotopomers of mevalonolactone (42) was developed (Scheme 4) 53 which is closely connected to some well-established approaches by Zamir and Nguyen. 54,55 The synthesis was designed to introduce deuterium in a flexible way from cheap reagents and make every position in compound 42 accessible.…”