Allylic Sulfones Containing Triene Moieties as Key Synthons for Carotenoid Synthesis

Abstract

An efficient synthetic method for the allylic sulfone 2 containing a conjugated triene moiety has been proposed involving i) coupling of allylic sulfones 4 with the C 5 bromoallylic sulfide 5, ii) base-promoted dehydrosulfonation in the presence of allylic sulfide, and iii) selective oxidation of the resulting trienyl sulfide to the corresponding sulfone. Total synthesis of lycopene starting from the C 15 allylic sulfone 2b has been described, where the new C 10 bis(chloroallylic) sulfone 11 proved to be a useful substitute for the C 10 bis(chloroallylic) sulfide 3, which did not require the problematic chemoselective sulfur oxidation in a conjugated polyene.Introduction. ± Carotenoids such as b-carotene (1a) and lycopene (1b) are characterized by long conjugated polyene chains that show distinctive red colors and are ideally utilized as nonhazardous dyes for foodstuffs. High reactivity of these polyenes with activated carcinogenic oxygen or radicals provides carotenoids with prophylactic effects against certain cancers of the pancreas, the mouth, and the bladder, etc.[1]. Among the numerous approaches that have appeared in the literature to build the conjugated polyene chains of carotenoids [2], methods based on acetylide coupling/ partial hydrogenation [3] and Wittig olefination [4] have been the two main synthetic approaches. The Julia sulfone olefination protocol [5], which has been applied to retinol synthesis [6], is presumed to be the best method to produce double bonds with the (E)-configuration [7]. We have introduced the C 10 bis(chloroallylic) sulfide 3 as a stable substitute for the highly unstable 1,8-dichloro-2,7-dimethylocta-2,4,6-triene, and successfully accomplished total syntheses of b-carotene (1a) and lycopene (1b) based on the Julia sulfone-olefination protocol [8]. To generalize this process with C 10 bis(chloroallylic) sulfide 3 for carotenoid syntheses, an efficient method should be devised to build allylic sulfones containing conjugated CC bonds such as 2 (Scheme 1). We herein report our strategy to synthesize allylic sulfones comprising a conjugated triene moiety and total synthesis of lycopene [9] by means of the allylic sulfone 2b.

Role of Ring Ortho Substituents on the Configuration of Carotenoid Polyene Chains

“…Typical disconnection approach to 9,9′,13,13′-tetramethylcarotene 1 was either using C 10 dihalide 3 or C 10 dialdehyde 4 (Scheme ). The functional group X of the coupling partner 2 may be selected among benzenesulfonyl (−SO 2 Ph), benzothiazolesulfonyl (−SO 2 BT), and triphenylphosphonium bromide (−PPh 3 Br) according to the olefination methods of Julia, Julia–Kocienski, and Wittig, respectively (Scheme ).…”

Systematic Synthesis of Diphenyl‐Substituted Carotenoids as Molecular Wires

“…with C 10 bis(chloroallylic) sulfone 8 (1 equiv. ), Ramberg–Bäcklund reaction, and dehydro‐desulfonation could possibly produce the desired carotenoids 2 and 3 .…”

Novel synthesis of pinacols and sulfones promoted by SmNiCl2 bimetallic system

“…Vinyl sulfone‐modified pyranoses and furanoses were unlimited and versatile source of chiral building blocks 27. Both allylic sulfones and the disulfone intermediates were the key synthons for carotenoid synthesis 28, 29. C15C25 fragment of sulfone was the key synthon for total synthesis of (+)‐lasonolide 30.…”