Synthesis of (+)‐Epoxydon, (–)‐Phyllostine, (–)‐RKTS 33, and (–)‐Parasitenone Featuring Selective Sulfonylation and Oxirane Ring Closure of Aldol Cyclization Products

Abstract

Two new synthetic approaches to anhydrogabosines are developed from the polyoxygenated aldol cyclization intermediates, bearing different O‐protecting groups, which were transformed to various gabosine‐type cyclitols. Selective sulfonylation on the required hydroxyl group of the intermediates and the subsequent oxirane ring closure are employed as the key steps in both approaches, by which (+)‐epoxydon, (–)‐phyllostine, (–)‐RKTS 33, and (–)‐parasitenone were synthesized from δ‐d‐gluconolactone.

Practical synthesis of ECH and epoxyquinols A and B from (−)-shikimic acid

“…After the first report and preparation of the bioactive molecule RKTS-33 by Kakeya and Osada, 7 a only two syntheses of its enantiomer ( ent -RKTS-33) were achieved. 19 All spectroscopic and spectrometric data for our synthesized sample were in good accord with the values reported in the literature. 7 a ,19 This result validated the S configuration of the C-4 hydroxyl group introduced via the stereoselective allylic oxidation of 15 .…”

“…19 All spectroscopic and spectrometric data for our synthesized sample were in good accord with the values reported in the literature. 7 a ,19 This result validated the S configuration of the C-4 hydroxyl group introduced via the stereoselective allylic oxidation of 15 .…”

Natural epoxyquinoids: isolation, biological activity and synthesis. An update

“…Phyllostine belongs to a class of naturally occurring cyclohexane epoxides – anhydrogabosines. 55 As a starting compound, Chen and colleagues, developing their strategy for the synthesis of bioactive natural products using commercial carbohydrates, chose δ- d -gluconolactone 15 as the starting compound for the synthesis of (−)-phyllostine (Scheme 5), 56 which was converted into a compound 16 by the known method. 57 Further aldol cyclization led to the formation of a 7 : 1 mixture of diastereoisomeric alcohols 17 , which were converted in (−)-phyllostine in 9 steps with an overall yield of 29%.…”

“…Epoxydon, RKTS 33 and parasitenone belong to a class of naturally occurring cyclohexane epoxides – anhydrogabosines. 55 δ- d -Gluconolactone 15 was converted to the key compound 17 (Scheme 12) 56 according to the method described earlier (see Section 3.2.3). 57 Compound 17 contains three types of hydroxyl protecting groups allowing different deprotection and functional group manipulation strategies to be used to obtain key compounds 54 (Scheme 12) and 55 (Scheme 13).…”