Asymmetrized Tris(hydroxymethyl)methane and Related Synthons: Enantioselective Preparation and Synthetic Applications

Abstract

Asymmetrized tris(hydroxymethyl)methane (THYM*) is a new chiral building block easily accessible in both enantiomeric forms by a chemoenzymatic methodology. The presence of three synthetically equivalent masked hydroxymethyl groups and a high degree of latent symmetry (C3v) makes this synthon very versatile in synthetic applications. This review describes its preparation and a series of elaborations (with particular enphasis on the diastereoselective generation of additional chiral centers) leading to advanced intermediated for the preparation of biologically active compounds.

Diversity oriented and chemoenzymatic synthesis of densely functionalized pyrrolidines through a highly diastereoselective Ugi multicomponent reaction

“…For the synthesis of 2, the route depicted in Scheme 2 was followed. Compound 6, a synthetic equivalent of desymmetrized trishydroxymethylmethane (THYM*), 20 was converted, under Mitsunobu conditions, into the key aryl ether 11. Three branch routes depart from this intermediate, two of them leading to (S)-2 (Route B and C) and one to (R)-2 (Route A).…”

“…[a] D ª 0 (c 2.0, CHCl 3 ). IR: n max (CHCl 3 )/cm (14), 200 (8.7), 199 (13), 198 (7.3), 178 (12), 175 (7.5), 174 (94), 173 (11), 172 (100), 157 (14), 155 (13), 145 (9.8), 143 (9.2), 120 (20), 119 (5.2), 94 (7.4), 93 (27), 92 (6.6), 86 (14), 76 (8.8), 75 (9.3), 68 (6.6), 65 (29), 64 (11), 63 (17), 57 (9.8), 56 (9.1), 55 (8.9), 54 (7.5), 50 (5.8), 44 (6.0), 42 (12), 41 (27), 39 (16), 38 (5.9). m/z (ESI-) 284.0028 (M -H + ).…”

“…Compound 16 was prepared from 16), 269 (14), 259 (13), 257 (12), 245 (5.4), 243 (6.1), 232 (7.4), 231 (54), 230 (7.5), 229 (52), 227 (5.6), 225 (6.0), 220 (20), 219 (5.4), 192 (5.5), 187 (5.7), 185 (5.9), 157 (7.9), 155 (7.3), 146 (22), 145 (19), 135 (5.7), 131 (7.5), 119 (5.5), 117 (100), 115 (16), 105 (6.1), 99 (9.1), 89 (12), 85 (6.9), 77 (10), 76 (13), 75 (80), 74 (5.9), 73 (38), 71 (6.4), 59 ( 16), 57 (6.0), 45 (6.3), 43 (90), 41 (15). m/z (ESI+) 439.0925 (M + Na + ).…”

“…A solution of (R)-or (S)-19 (123 mg, 306 mmol) in dry CH 2 Cl 2 (2.5 mL) was cooled to -30 (8.5), 326 (43), 301 (6.5), 299 (6.7), 271 (12), 269 (11), 259 (11), 257 (10), 233 (5.0), 232 (14), 231 (100), 230 (15), 229 (96), 220 (7.7), 187 (23), 185 (24), 180 (6.0), 179 (5.5), 157 (14), 155 (14), 151 (5.1), 150 (9.4), 149 (7.9), 146 (6.5), 139 (9.7), 137 (9.6), 135 (12), 131 (6.0), 127 (9.9), 115 (13), 114 (24), 99 (9.4), 89 (6.7), 86 (5.0), 85 (11), 84 (39), 78 (5.4), 77 (7.3), 76 (20), 75 (34), 74 (6.0), 73 (46), 71 (11), 64 (5.2), 63 (6.7), 59 (25), 58 (10), 57 (12), 55 (5.7), 53 (5.1), 47 (6.6), 45 (12), 43 (14), 41 (37), 39 (10). m/z (ESI+) 406.0795 (M + Na + ).…”

The α,α-Difluorinated Phosphonate L-pSer-Analogue: An Accessible Chemical Tool for Studying Kinase- Dependent Signal Transduction

“…The Tokyo route and our second generation triflate displacement route also share the advantage of permitting N-carbamate deprotection, in situ, though in different ways. Interestingly, since the original Shibuya route was published, studies by Guanti and coworkers (Banfi and Guanti, 1998; Banfi et al, 2005), in particular, have produced a number of methods for tris(hydroxymethyl)methane desymmetrization. So, one should be able to enter this triflate displacement route with a single antipode of this type of THYM educt.…”