A new efficient method for the stereoselective preparation of trans‐2,5‐bis(alkyloxymethyl)pyrrolidines ( 7 ) using easily available starting materials is described. The main step of this synthesis is the stereoselective formation of the pyrrolidine ring by the 1,3‐dipolar cycloaddition reaction of an in situ generated azomethine ylide. Both enantiomers of the C2‐symmetric auxiliaries are prepared separately in a short reaction sequence. 相似文献
Substituted 2‐tropolone natural products are found in plants and fungi. Their biosynthesis is thought to occur by ring expansion from a cyclohexadienone precursor, but this reaction has not previously been demonstrated experimentally. Treatment of 6‐hydroxy‐6‐hydroxymethylcyclohexa‐2,4‐dienone with the non‐haem iron(II)‐dependent extradiol catechol dioxygenase MhpB from Escherichia coli results in the formation of the 2‐tropolone ring‐expansion product through a pinacol‐type rearrangement. Three further substituted cyclohexa‐2,4‐dienone analogues were prepared, and treatment of each analogue was found to give the substituted 2‐tropolone ring‐expansion product. This ring expansion could also be effected nonenzymatically by treatment with 1,4,7‐triazacyclononane and FeCl2. This is a novel transformation for non‐haem iron‐dependent enzymes, and this is the first experimental demonstration of the proposed ring‐expansion reaction in tropolone biosynthesis.相似文献
A variety of epoxy polyene terpenes cyclize readily by confinement within zeolite NaY to form primarily products of monocyclization. The monocyclization pathway is highly predominant, irrespectively of the side chain of the epoxy terpene, while the monocyclic products possess regioselectively an exomethylenic double bond. The selective monocyclization in the case of epoxyfarnesyl acetate, epoxyfarnesylacetone or 2,3‐epoxysqualene, provides a direct route to the synthesis of a variety of natural products, such as elengasidiol, farnesiferols B–D, achilleol A, camelliol C and to four farnesylacetone‐derived metabolites isolated from the brown algae Cystophora monoliformis. The optical rotation of achilleol A derived from the cyclization of (S)‐2,3‐epoxysqualene matches with that of the natural product, thus the absolute configuration of achilleol A was established as 1S,3R. From the mechanistic point of view, the NaY‐promoted cyclization of 9,10‐epoxygeranylacetone, selectively deuterium labelled at the C‐10 methyl group, is >97% stereoselective with respect to the topicity of the gem‐dimethyl group. This result is in agreement with a concerted mechanism. Finally, we have proved through labelling experiments, for the first time, that the biomimetic transformation of epoxy polyene terpenes to 2,3,4‐trimethylcyclohexanones upon acid catalysis is a highly stereoselective process. Thus, the less hindered gem‐methyl group on the epoxide functionality becomes α‐ to the carbonyl in the final isomerized product. 相似文献
Cytochrome P450 BM3 monooxygenases are able to catalyze the regio‐ and stereoselective oxygenation of a broad range of substrates, with promising potential for synthetic applications. To study the suitability of P450 BM3 variants for stereoselective benzylic hydroxylation of 2‐alkylated benzoic acid esters, the biotransformation of methyl 2‐ethylbenzoate, resulting in both enantiomeric forms of 3‐methylphthalide, was investigated. In the case of methyl 2‐propylbenzoate as a substrate the regioselectivity of the reaction was shifted towards β‐hydroxylation, resulting in the synthesis of enantioenriched R‐ and S‐configured 3‐methylisochroman‐1‐one. The potential of P450 BM3 variants for regio‐ and stereoselective synthesis of phthalides and isocoumarins offers a new route to a class of compounds that are valuable synthons for a variety of natural compounds. 相似文献
Diterpenes form a vast and diverse class of natural products of both ecological and economic importance. Class II diterpene synthase (diTPS) enzymes control the committed biosynthetic reactions underlying diterpene chemical diversity. Homology modelling with site‐directed mutagenesis identified two active‐site residues in the horehound (Marrubium vulgare) class II diTPS peregrinol diphosphate synthase (MvCPS1); residue substitutions abolished the unique MvCPS1‐catalysed water‐capture reaction at C9 and redirected enzyme activity toward formation of an alternative product, halima‐5(10),13‐dienyl diphosphate. These findings contributed new insight into the steric interactions that govern diTPS‐catalysed regiospecific oxygenation reactions and highlight the feasibility of diTPS engineering to provide a broader spectrum of bioactive diterpene natural products. 相似文献
Mannopeptimycin, a potent drug lead, has superior activity against difficult‐to‐treat multidrug‐resistant Gram‐positive pathogens such as methicillin‐resistant Staphylococcus aureus (MRSA). (2S,3S)‐β‐Methylphenylalanine is a residue in the cyclic hexapeptide core of mannopeptimycin, but the synthesis of this residue is far from clear. We report here on the reaction order and the stereochemical course of reaction in the formation of (2S,3S)‐β‐methylphenylalanine. The reaction is executed by the enzymes MppJ and TyrB, an S‐adenosyl methionine (SAM)‐dependent methyltransferase and an (S)‐aromatic‐amino‐acid aminotransferase, respectively. Phenylpyruvic acid is methylated by MppJ at its benzylic position at the expense of one equivalent of SAM. The resulting β‐methyl phenylpyruvic acid is then converted to (2S,3S)‐β‐methylphenylalanine by TyrB. MppJ was further determined to be regioselective and stereoselective in its catalysis of the formation of (3S)‐β‐methylphenylpyruvic acid. The binding constant (KD) of MppJ versus SAM is 26 μM . The kinetic constants with respect to kcat Ppy and KM Ppy, and kcat SAM and KM SAM are 0.8 s?1 and 2.5 mM , and 8.15 s?1 and 0.014 mM , respectively. These results suggest SAM has higher binding affinity for MppJ than Ppy, and the C? C bond formation in βmPpy might be the rate‐limiting step, as opposed to the C? S bond breakage in SAM.相似文献
Highly regio‐ and stereoselective formation of allylamines has been achieved through a three‐component reaction between iodobenzene, an allene, and an amine in acetonitrile, catalyzed by in situ formed and by isolated palladium‐diphosphine catalysts. 相似文献
An efficient protocol for the highly regio‐ and stereoselective synthesis of 4‐(3′‐hydroxy‐2′‐iodoalk‐1′(Z)‐enyl)furan‐2(5H)‐one derivatives via selective iodohydroxylation of non‐heteroatom‐substituted allenes, i.e., 4‐allenyl‐2(5H)furanones, has been developed. The regio‐ and stereoselectivity of this reaction may be controlled by the electronic and steric effects of the furanone ring. 相似文献
(R)‐Benzoins and (R)‐2‐hydroxypropiophenone derivatives are formed on a preparative scale by benzaldehyde lyase (BAL)‐catalyzed C−C bond formation from aromatic aldehydes and acetaldehyde in aqueous buffer/DMSO solution with remarkable ease in high chemical yield and high optical purity. The substrate range of this thiamin diphosphate‐dependent enzyme was examined with respect to a broad applicability of this benzoin condensation‐type reaction in stereoselective synthesis. 相似文献
A novel nickel(II)‐magnesium‐mediated cross‐coupling of diphenylphosphine oxide with a variety of 1,1‐dibromo‐1‐alkenes has been developed, which provides a powerful and general methodology for the stereoselective synthesis of various (E)‐1‐alkenylphosphine oxides or bisphosphine oxides, with operational simplicity of the procedure, good to high yields and broad substrate applicability. Mechanistic studies reveal that the reaction might involve a Hirao reduction, cross‐coupling and Michael addition. 相似文献
Polar meso‐tetraarylporphyrins 2 – 4 were synthesized from tetrakis‐4‐hydroxyphenylporphyrin 1 as the central building block by consecutive base‐induced reactions with glycidol. The decorating units form a polar hydrogen‐bonded shell around the sensitizer core which is proposed as the binding site for polar substrates in photocatalyzed oxygenation reactions. As substrate, the polarity‐sensor mesitylol ( 5 ) was applied and the reaction constrained in a polystyrene matrix. Increasing shell dimensions lead to increased diastereoselectivities for the allylic hydroperoxides 6 and thus clearly demonstrate the concept of shell‐induced substrate stereoselectivity in singlet oxygen reactions. 相似文献
Both cis‐ and trans‐but‐2‐ene‐1,4‐diamines have been prepared and efficiently applied as sacrificial cosubstrates in enzymatic transamination reactions. The best results were obtained with the cis‐diamine. The thermodynamic equilibrium of the stereoselective transamination process is shifted to the amine formation due to tautomerization of 5H‐pyrrole into 1H‐pyrrole, achieving high conversions (78–99%) and enantiomeric excess (up to >99%) by using a small excess of the amine donor. Furthermore, when the reaction proceeded, a strong coloration was observed due to polymerization of 1H‐pyrrole. A structurally related compound, cis‐but‐2‐ene‐1,4‐diol, has been utilized as cosubstrate in different alcohol dehydrogenase (ADH)‐mediated bioreductions. In this case, high conversions (91–99%) were observed due to a lactonization process. Both strategies are convenient from both synthetic and atom economy points of view in the production of valuable optically active products.