Studies on Hot Water Extract of Mycobacterium tuberculosis. I. Structural Analyses of Polysaccharides

Synthesis of a Lipomannan Component of the Cell‐Wall Complex ofMycobacterium tuberculosisIs Based on Paulsen's Concept of Donor/Acceptor “Match”

“…[2] Significant interest stems from recent discoveries showing that LAM exhibits a profound propensity toward immunomodulation, [3] the ability to enhance resistance to various cancers [4,5] and herpes, [6] and a surprising capacity to potentiate HIV antiretroviral drugs. [7] This multifaceted biological profile is matched by its multifaceted architecture, [8] shown as compound 1 by Turnbull Bn = benzyl, Bz = benzoyl, DMAP = 4-(dimethylamino)pyridine; DMF = N,N-dimethylformamide; py = pyridine; TBAI = tert-butylammonium iodide; TBAF = tert-butylammonium fluoride; TBDMS = tertbutyldimethylsilyl, TBDPS = tert-butyldiphenylsilyl, TCA = trichloroacetyl, Tr = trityl.…”

“…However, if Yb(OTf) 3 is used for the latter purpose, NPOEs are chemoselectively activated [14,15] without affecting disarmed or armed n-pentenyl glycosides (NPGs) such as 4a and 4b. Alternatively, the hydrolysis of an NPOE gives a protected mannose (for example, 3d!4d), which opens a facile route to popular trichloroacetimidate donors such as 4e, which can also be activated by Yb(OTf) 3 . [15,19] Scheme 2.…”

“…This forced us to investigate an alternate route that involved the tritylated analogue 8. Accordingly, pseudodisaccharide 6 b, prepared in 97 % yield from diol 5 and excess NPOE 3 f, was treated with armed NPG 4 b and Sc(OTf) 3 / NIS. The near quantitative yield (94 %) of 8, supports the "match" between the armed donor 4 b and the inositol-2-OH.…”

“…Iteration of the last two steps, but with Yb(OTf) 3 to ensure regioselective glycosidation at the primary hydroxy group, led to triol 11 b, tetraol 11 c, and pentaol 11 d, with excellent yields maintained throughout. The structure of 11 d was supported by resolved signals in the 13 13 C NMR spectra, consistent with the 11 pyranoside residues.…”

“…1 a) 3 e, Yb(OTf) 3 , NIS, CH 2 Cl 2 , 1 b) NaOMe, MeOH, CH 2 Cl 2 ; 2) NaOMe, MeOH, CH 2 Cl 2 ; 3) NaH, BnBr, TBAI, DMF; 4) TBAF, MS, THF; 5) stearoyl chloride, DMAP, py, CH 2 Cl 2 .…”