Synthesis of Enantiopure 2-C-Methyl-d-erythritol 4-Phosphate and 2,4-Cyclodiphosphate from d-Arabitol

Abstract

[reaction: see text] Two key intermediates of the newly discovered mevalonate-independent pathway for isoprenoid biosynthesis were prepared. Optically pure 2-C-methyl-D-erythritol 4-phosphate and 2,4-cyclodiphosphate were chemically synthesized from D-arabitol using a convenient benzylidene and tert-butyldimethylsilyl protection of polyhydroxylated intermediates. The new scheme offers a straightforward route to analogues and labeled forms.

Effect of temperature on d-arabitol production from lactose by Kluyveromyces lactis

“…D-Arabitol is a naturally occurring pentitol with a relatively low degree of sweetness and is found in body fluids [4]. Recently, D-arabitol has been used as a raw material, either for the chemical synthesis of enantiopure compounds, immunosuppressive glycolipids, herbicides, and antipathogenic-disease medicines [5][6][7], or for the biological production of another pentitol, xylitol [8][9][10][11]. D-Arabitol is a key compound selected as one of the 12 potent building-block chemicals for biorefinery by the Department of Energy in the United States [12].…”

Physical state of 2-methylbutane-1,2,3,4-tetraol in pure and internally mixed aerosols

“…For our study, we needed 2-methylbutane-1,2,3,4-tetraol (tetraol) in gram amounts as racemates and as enantiomerically enriched materials of all of its four stereoisomers. Because of their importance in biological and atmospheric research the syntheses of the stereoisomers of tetraol have been devised already (Cole-Filipiak et al, 2010;Duvold et al, 1997;Ebben et 20 al., 2014;Enders et al, 2007;Fontana et al, 2000;Ghosh et al, 2012;Giner et al, 2002;Hoeffler et al, 2000;Koumbis et al, 2007;Moen et al, 2007;Robinson et al, 2009;Sharma et al, 2008;Urbansky et al, 2004). Among the reported syntheses, the reports of Ghosh et al (Ghosh et al, 2012), Moen et al, (Moen et al, 2007) and Sharma et al (Sharma et al, 2008) appeared most attractive to us as they show an access to both diastereomers through the same reaction sequence and give the four stereoisomers as stereochemically highly homogeneous materials with enantiomeric excesses (ee) of 80-99%.…”

Bioconversion of Lignocellulose: Inhibitors and Detoxifi cation

“…Coates and coworkers have reported a versatile synthesis of ME, MEP and cMEPP from D-arabitol as the starting material [65,66]. In the authors' strategy, benzylidene-protected D-arabitol 58 was first converted to 1,3-benzylidene-D-threitol 59 and subsequently transformed to (2S,4R)-cis-2-phenyl-4-tert-butyldimethylsilyloxy-1,3-dioxan-5-one 61 in two steps.…”

“…Enantiopure preparations of MEP as the sodium salt from 1,2:5,6-di-O-isopropylidene-D-mannitol proceeded in 9% yield over 14 steps (as compared to 32% over 7 steps) [72] and preparation of the free acid from 1,2-O-isopropylidene--D-xylofuranose proceeded in 32% yield over 7 steps (compared to 27% yield over 5 steps) [64]. More recent syntheses from carbohydrate-based starting material have also provided facile access to other metabolites based on an ME backbone (such as MEP or cMEPP) [65,66] or in the synthesis of derivatives of MEP [73] via hydrogenation followed by treatment with ammonia provided MEP as the ammonium salt in good yield 71 (Scheme 16) [65].…”

“…A phase-transfer-promoted RuO 4 oxidation provided ketone 99 followed by reduction with methylmagnesium bromide 100 and removal of the protecting group yielding the benzylidene protected ME 101. Double phosphorylation using phosphoramidite coupling instilled the two benzyl-protected phosphate esters 102 and selec- tive debenzylation of the phosphate esters via hydrogenation provided the bis-phosphomonoester 103, which was subsequently cyclized using 1, 1'-carbonyl diimidazole to provide the penultimate intermediate 104 [65,66]. The final product, cMEPP 95, was generated by simple hydrogenation over palladium hydroxide (Scheme 21).…”