Stereoselective Synthesis of Enantiopure Oxetanes, a Carbohydrate Mimic, an ϵ‐Lactone, and Cyclitols from Biocatalytically Derived β‐Hydroxy Esters as Chiral Precursors

Abstract

Biocatalytically derived enantiopure α‐substituted β‐hydroxy esters serve as excellent chirons for the synthesis of a diverse set of structures such as oxetanes, a carbohydrate mimic, an ϵ‐lactone, and carbocyclic and aromatic cyclitols. The starting materials can be easily accessed in enantiopure form from α‐substituted β‐keto esters by biocatalytic reduction with Klebsiella pneumoniae (NBRC 3319). Ring‐closing metathesis (RCM) is one of the key transformations used to create the carbocyclic/heterocyclic frameworks reported in this article. The synthesized cyclitols were screened for their inhibitory effect on α‐ and β‐glucosidases.

Recent Advances in Synthetic α‐Glucosidase Inhibitors

“…Compound 50 shows excellent inhibitory activity against baker's yeast aglucosidase. [28] Compounds 54 and 55,d esignedo nt he basis of polyhydroxycyclohexane, show better inhibitory activity against baker's yeast a-glucosidase than DNJ, though they have no effect on rice a-glucosidase. Amonga ll of the N1-substituted derivatives of 50,c ompound 51 displays the highest inhibitory activity.…”

“…[27] However,t heir isomersa nd aryl-substituted derivatives possess poor inhibitory activity. [28] Compounds 54 and 55,d esignedo nt he basis of polyhydroxycyclohexane, show better inhibitory activity against baker's yeast a-glucosidase than DNJ, though they have no effect on rice a-glucosidase. SAR studies indicatet hat the position of the amino and hydroxy groups is crucial for their inhibitory activity,a nd the lipid chain is also ac ritical structure.…”

Syntheses and Antibacterial Evaluation of New Penicillium Metabolites Gregatins G and Thiocarboxylics C

“…However, thiocarboxylic C 1 (3a) was obtained with an excellent yield of 96 % upon treating silyl ether 16b with 80 equivalents of HF-pyridine (entry 9). [21] Related to starting vinyl bromide 8, thiocarboxylic C 1 (3a) was obtained with an overall yield of 25 % when using a TBDPS protecting group, and with a mere 4 % yield when using a MEM group. Gregatin G 1 (6a) was synthesised with a total yield of 6 % (MEM) and 17 % (TBDPS).…”

“…The values for gregatin G 1 (6a) and G 2 (6b) also differed from those of the isolate. The values of the isolates with a ½ � 20 D = + 177 (c = 0.1, CHCl 3 ) [8] for 6a and a ½ � 20 D = 1 [16] 14a (A) 6a 23 2 [17] 14a (B) 6a 11 3 [18] 14a (C) 6a 32 4 [16] 16a (A) 3a -5 [19] 16a (D) 3a -6 [18] 16a (C) 3a 22 7 [20] 14b (E) 6a 64 8 [20] 16b (E) 3a -9 [21] 16b + 171 (c = 0.1, CHCl 3 ) [8] for 6b are higher than the values of our synthetic compounds with a ½ � 25 D = + 96 (c = 0.50, CHCl 3 ) for 6a and a ½ � 25 D = + 104 (c = 1.00, CHCl 3 ) for 6b. These deviations might be due to impurities of the isolated compounds as visible in their 1 H-NMR spectra.…”

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…224) [575], transpentacin derivatives [576], bis spirocyclopentenes [577], nardoaristolone B and analogs [578], cyclaradine [579], carbocyclic nucleoside analogs [580], cyclopentenefused nucleosides [581], cyclopentenols for the preparation of enantio enriched 4-hydroxy-2-cyclopentenones [582], and failure to form a five-membered ring bridge of a nucleoside derivative by RCM [583]; (2) cyclopentenes and dihydrofurans [584]; (3) α,β-unsaturated cyclopentenones [585], including those employed in syntheses of TEI-9826 [586]; (4) five-and six-membered ring alkenes substituted by electron-withdrawing groups [587]; (5) five-and six-membered rings fused (spiro or regular fusion) to indole systems [588]; (6) fiveand six-membered rings spiro fused to a 1,2-diphenylpyrazolidine-3,5-dione ring system [589]; (7) five-to seven-membered ring carbocycles and oxygen heterocycles using biocatalytically-derived starting materials [590]; (8) five-to seven-membered ring carbocycles [591]; (9) five-to seven-membered ring carbocyclic and heterocyclic vinylboronates (e.g. 225) [592]; (10) cyclohexenes, including those employed in syntheses of fluorinated inositol analogs [593], fluorinated cyclohexenes [594], lundurine B (the enol ether was converted to the ketone without isolation) (e.g.…”