Synthesis and stereochemistry of (−)-rosiridol and (−)-rosiridin

Total Syntheses of Rhodiolosides A and D and of Sachalinols A–C

“…The picture is different with regard to the absolute stereochemistry of sachalinols B and C. Synthetic (+)-sachalinol C exhibits a positive optical rotation {7, [α] D 29 = +47.0 (c = 0.06, MeOH)}, which is in agreement with the value reported {[α] D 25 = +40.2 (c = 0.05, in MeOH)} for the natural product (+)-sachalinol C. [6] Because the configuration of our synthetic product at C-4 is known, the absolute configuration of the natural product (+)-sachalinol C (7) must be revised to (4S), as has already been necessary for (-)-sachalinol A (3, vide supra) and (-)-rosiridol (1). [9] However, the sense of rotation of the synthesized (-)-sachalinol B {6, [α] D 24 = -29.2 (c = 0.24, MeOH)} is the opposite of that of the natural product (+)-sachalinol B {ent-6, [α] D 25 = +60.3 (c = 0.07, in MeOH)} reported by Kadota. [6] To verify that the synthesized compounds 6 and 7 are epimeric only at C-6 and share the same configuration at C-4, we converted the mixture of the TBDPS-protected precursors 28 and 29 into the corresponding mixtures of (R)and (S)-Mosher esters.…”

“…[9] However, the sense of rotation of the synthesized (-) [6] To verify that the synthesized compounds 6 and 7 are epimeric only at C-6 and share the same configuration at C-4, we converted the mixture of the TBDPS-protected precursors 28 and 29 into the corresponding mixtures of (R)-and (S)-Mosher esters. In both cases, mixtures of only two products were obtained, which confirms that the diastereomers 28 and 29 are enantiomerically pure and that no partial racemization had occurred on formation of the tetrahydrofuran ring.…”

“…The starting material 8 (Scheme 1) was synthesized as described earlier. [9] For the enantioselective reduction of 8, we replaced DIP-Cl by the CBS reagent [(+)-(R)-2-methyl-CBS-oxazaborolidine], [15] which provided the secondary alcohol 9 in a higher yield (66 % in comparison with 44 %) though with a slightly lower ee (90 % in comparison with 94 %). Mosher analysis [16] of 9 confirmed the stereochemical outcome of the CBS reduction, with the prenyl group functioning as the smaller substituent.…”

“…[5] (-)-Rosiridin (2) is the β-glucosylated analogue of (-)-rosiridol (1) [6] and has recently been identified as an inhibitor of monoamine oxidase B (MAO B), which is involved in neurodegenerative diseases. [7] After contradictory assignments, the stereochemistry of the monoterpenoid sections of (-)-rosiridol (1) and (-)-rosiridin (2) was established as (4S) by total synthesis [8,9] and by reinvestigation of the isolated natural products. [10,11] In this paper we describe the first total syntheses of (-)-rhodioloside A (4), (-)-rhodioloside D (5, Scheme 4, below), (-)-sachalinol B (6, Scheme 5, below), and (+)-sachalinol C (7, Scheme 5, below).…”

“…UV/Vis (MeOH): λ max (lg ε) = 204 (4.47) nm. MS (EI): m/z (%) = 367 (2), 289 (9), 199 (100), 139 (21), 43 (21). HRMS (EI): calcd.…”