Facile Syntheses of Valiolamine and Its Diastereomers from (−)-Quinic Acid.¹ Nucleophilic Substitution Reactions of 5-(Hydroxymethyl)cyclohexane-1,2,3,4,5-pentol

Abstract

Valiolamine (1), 1-epi-valiolamine (2), 2-epi-valiolamine (3), (1R,2R)-valiolamine (4), and 2-amino regioisomer 17 have been prepared from (−)-quinic acid (6) in 14 (8.4% overall yield), 13 (9.0%), 15 (4.3%), 17 steps (2.5%), and 12 steps (13%), respectively. Charged nucleophilic ring-openings of cyclic sulfate (1R,2S,3S,4S,5S)-4,5-di-O-acetyl-3-O-benzyl-5-(benzyloxymethyl)-1,2-O,O-sulfonylcyclohexane-1,2,3,4,5-pentol (11) occurred regioselectively at C-2, whereas the corresponding ring-openings of its (1S,2R)-diastereomer 34 proceeded preponderantly at C-1. (1R,2S,3R,4S,5S)-2,4,5-Tri-O-acetyl-3-O-benzyl-5-((benzyloxy)methyl)-1-O-(trifluoromethanesulfonyl)cyclohexane-1,2,3,4,5-pentol (24) underwent novel internal displacement spontaneously to form (1S,2S,3R,4S,5S)-1,2,4-tri-O-acetyl-3-O-benzyl-5-((benzyloxy)methyl)cyclohexane-1,2,3,4,5-pentol (25), whereas its 2-epimer was inert under the same conditions. Ruthenium-catalyzed dihydroxylation of alkene, (3R,4S,5S)-4,5-O-acetyl-3-O-benzyl-5-((benzyloxy)methyl)-1-cyclohexene-3,4,5-triol (31), gave the desired β-1,2-diol 32 in higher yield and stereoselectivity than the osmium tetraoxide protocol. The regioselectivity of charged nucleophilic ring-openings of cyclic sulfates 11, 34, and 38 is discussed.

A C2‐Symmetric Pool Based Flexible Strategy: An Enantioconvergent Synthesis of (+)‐Valiolamine and (+)‐Valienamine

“…Finally, reductive cleavage of the epoxide and the N ‐benzyl group in carbamate 11 with Li/NH 3 followed by LiOH‐promoted carbamate hydrolysis and HOAc‐assisted acetal deprotection resulted in efficient formation of 1 . Comparison of the physical properties of the N,O‐acetyl derivative of 1 to those recorded confirmed its identity 4c,15. By simple modification of the reaction conditions, we found that this one‐pot reductive cleavage, deprotection, and acylation sequence under conditions reported by Trost16 proceeded in 53 % overall yield in a single vessel without isolation of any intermediates.…”

“…[ α ] D 25 = –19.6 ( c = 0.2, CHCl 3 ) {ref 15. [ α ] D 20 = –18.0 ( c = 1.0, CHCl 3 ), ref 4c. [ α ] D 20 = –17.8 ( c = 2.0, CHCl 3 ), ref 2b.…”

Recent Advances in the Chemistry of Aminocyclitols

“…Several natural products containing polyhydroxycyclohexane skeletons, such as vibo ‐quercitol, quinic acid, or cyclophellitol (Figure 4), have frequently been used as starting materials in the syntheses of aminocyclitol derivatives. Classical examples are to be found in the syntheses of valiolamine20 and related amino‐carbasugars21 from quinic acid, the syntheses of (–)‐valiolamine and (–)‐1‐epi‐valiolamine from vibo ‐quercitol,22 and the total syntheses of (+)‐validamycin B and (+)‐validoxylamine B from cyclophellitol derivatives 23…”

Synthesis of a Novel Benzoyl Adenosine Analog Containing a 1, 4-Dioxane Sugar Analog and the Synthesis of a Corresponding Uracil Adenine Dinucleotide

“…A number of literature methods described were tested [19,20], such as cleavage using 80% acetic acid [21] or CSA as catalyst, reaction with Amberlyst 15, HCl [22] or trifluoroacetic acid [23]. Other reagents, such as ferric chloride on silica gel [24], iodine in methanol [25] or alumina or silica gel catalysis in all cases gave no or similar results.…”