Facile Syntheses of All Possible Diastereomers of Conduritol and Various Derivatives of Inositol Stereoisomers in High Enantiopurity from myo-Inositol

Abstract

Phosphoinositide-based signaling processes are crucially important in intracellular signal transduction events. Inositol phosphate analogues have been useful in probing the structure-activity relationships between inositol phosphates and biomacromolecules, and in studying biological functions of newly found inositol phosphates. Thus, a systematic and ready access to inositol stereoisomers is highly desirable. And practical and convenient syntheses of conduritols and related compounds are also important because of their biological activities and their synthetic utilities in the preparation of other bioactive molecules. We herein report the first syntheses of all possible diastereomers of conduritol and various derivatives of eight inositol stereoisomers in high enantiopurity from myo-inositol, which involve efficient enzymatic resolution of the intermediates conduritol B and C derivatives, followed by oxidation-reduction or the Mitsunobu reaction, and cis-dihydroxylation in stereo- and regioselective manners.

Useful access to enantiomerically pure protected inositols from carbohydrates: the aldohexos-5-uloses route

“…There are three general synthetic approaches to prepare inositols: 1) stereoselective elaborations of the inexpensive, commercially available myo -inositol [8–13]; 2) elaboration of the six carbon atom skeleton of either a) tetrahydroxycyclohexene derivatives [14–15] (synthetic or natural conduritols) through stereoselective cis-hydroxylation or epoxidation–hydrolysis of the double bond or b) benzene [16–17] or halo-benzenes [18–21], by microbial oxidation; 3) carbocyclization involving organometallic intermediates (Ferrier II reaction [22] performed on 6- O -acyl-hex-5-enopyranosides followed by reduction [23–24]; trialkylaluminium [25–26] or titanium(IV)-assisted [27] conversion of hex-5-enopyranosides and SmI 2 -promoted [28–30] pinacol coupling of dialdehyde derivatives).…”

Enantioselective Synthesis of Natural Polyoxygenated Cyclohexanes and Cyclohexenes from [(p‐Tolylsulfinyl)methyl]‐p‐quinols

“…mCPBA oxidation of the sulfoxide to the sulfone (98 %) was followed by stereoselective DIBALH reduction (99 %), secondary OH protection and elimination of MeSO 2 pTol (Cs 2 CO 3 , 87 % for the two steps) to give the cyclohexenone (4S,6R)-24, [12] while epoxidation under the conditions described above (Ph 3 The synthesis of the other natural target bearing a cyclohexane structure-(À)-gabosine O (6)-only required the diastereoselective cis-dihydroxylation of the double bond of cyclohexenone (4R,6S)-24 and deprotection of the alcohol (Scheme 6). When (4R,6S)-24 was treated with RuCl 3 / NaIO 4 , [44] however, an inseparable 58:42 mixture of diaste- The p-facial diastereoselectivities of OsO 4 dihydroxylations are normally governed by steric factors, [17,45] and the bulky OTBDMS protecting group in 24 was slightly favouring dihydroxylation anti to the vicinal OTBDMS substituent. On the other hand, the diastereoselectivity of OsO 4 dihydroxylation of free allylic cyclohexenols has been shown to be dependent on the reactive conformation and the possibility of hydrogen bonding.…”

Regioselective SN2' Mitsunobu reaction of Morita–Baylis–Hillman alcohols: A facile and stereoselective synthesis of α-alkylidene-β-hydrazino acid derivatives

“…The alternative S N 2 displacement of the oxophosphonium moiety of 9 by the species 10 may be retarded by steric hindrance. Recently, S N 2' Mitsunobu reactions [31–32 39–45] have attracted considerable interest from the organic chemistry community due to their great synthetic potential being complementary to the Mitsunobu reactions. This report accordingly adds to a new valuable example of S N 2' Mitsunobu reactions.…”