Biocatalytic Asymmetric Rearrangement of a Methylene‐Interrupted Bis‐epoxide: Simultaneous Control of Four Asymmetric Centers Through a Biomimetic Reaction Cascade

Abstract

Asymmetric enzyme-catalyzed hydrolysis of methylene-interrupted bis-epoxides 1 a and 1 b catalyzed by bacterial epoxide hydrolases furnished tetrahydrofuran derivatives 2 a and 2 b through a hydrolysis-rearrangement cascade. Whereas racemic bis-oxiranes 1 b-d underwent kinetic resolution with moderate stereoselectivities to yield products with up to 92 % ee and 66 % de: meso-bis-oxirane cis,cis-1 a was transformed into (6R,7R,9S,10S)-2 a in 94 % ee and 89 % de at high conversion (85 %) by Rhodococcus sp. CBS 717.73 as the major product. The reaction sequence resembles a biomimetic reaction cascade and provides an efficient entry into the structural core of annonaceous acetogenins with simultaneous control of four stereocenters.

Synthesis and Cannabinoid Receptor Activity of Ketoalkenes from Echinacea pallida and Nonnatural Analogues

“…TLC was performed on alumina plates coated with silica gel (Merck silica gel 60 F 254 , thickness 0.2 mm) and products were detected after staining with 15 % phosphomolybdic acid in ethanol. NMR spectra were recorded with Bruker Avance 300 ( 1 H: 300.1 MHz, 13 The following compounds were prepared as described above and have been reported before: 1-methylcycloheptanol (13), [22] 8-bromooctan-2one (14), [17] 2-(6-bromohexyl)-2-methyl-1,3-dioxolane (15), [23] [24] 6-(2-methyl-1,3-dioxolan-2-yl)hexanal (11), [16] (Z)-hex-2-enyl acetate (17), [25] 2-(oct-2-ynyloxy)-tetrahydro-2H-pyran (19), [26] (Z)-oct-2-en-1-ol, [27] (Z)-hex-4-en-2-yn-1-ol (24), [28] (2E,4Z)-hexa-2,4-dien-1-ol (25), [28] ( (29), [29] (2Z,4E)-hexa-2,4-dien-1-ol. [30] General procedure A for the semi-reduction of alkynes to the corresponding (Z)-alkenes: Borane/dimethylsulfide complex (1.1 equiv) was added to dry Et 2 O (% 1 m) and cooled to 0 8C.…”

“…= 7.6 Hz, 2 H, CH 2 ; H(3)), 1.23 (q, 3 J = 7.5 Hz, 2 H, CH 2 ; H(5)), 1.14-1.09 ppm (m, 2 H, CH 2 ; H(4));13 C NMR (75 MHz, CDCl 3 ): d = 209.3 (C quat ), 132.2 (+), 130.7 (+), 129.3 (+), 127.1 (+), 125.6 (+), 124.4 (+), 43.7 (À), 30.6 (À), 29.9 (+), 29.4 (À), 28.8 (À),27.0 (À),23.7 (À), 13.3 ppm (+); IR (neat): ñ = 3014, 2932, 2856, 1716, 1358 cm À1 ; CI-MS (NH 3 ): m/z (%): 238 (100) [M+NH 4 + ]. 2-Methyl-2-((6Z,9Z,11E)-trideca-6,9,11-trienyl)-1,3-dioxolane (32): The compound was prepared following general procedure D and isolated as colourless oil.…”

Epoxide hydrolase-mediated enantioconvergent bioconversions to prepare chiral epoxides and alcohols

“…CBS 717.73 has been used for asymmetric rearrangement of a methyleneinterrupted bis-epoxide to THF derivatives as the single enantiomer with up to 94%ee at 85% conversion ( Fig. 4c) (Glueck et al 2004). Annonaceous acetogenins possessing a THF structure with four stereocenters have attracted commercial interests due to their biological activities such as antitumor, antimicrobial, and etc.…”

Epoxide‐Opening Cascades in the Synthesis of Polycyclic Polyether Natural Products

“…[5] This strategy was later extended into a general method for the synthesis of substituted tetrahydrofuran rings, and it is often used in preparation of biologically relevant molecules, such as nucleosides, and natural and unnatural monosaccharides. [169][170][171][172][173][174][175][176][177][178] Other early reports on epoxide-opening cascades were focused on rearrangements of topologically interesting molecules. In their pursuit of a postulated [2s+2s+2s] to [2s+2s+2s] sigmatropic rearrangement, the groups of Simmons [179,180] and Paquette [181,182] independently reported the transformation of triepoxide 64 to hexaquinane 65 under acidic conditions (Scheme 3).…”