1,4-Butanediol (BDO) is an important commodity chemical used to manufacture over 2.5 million tons annually of valuable polymers, and it is currently produced exclusively through feedstocks derived from oil and natural gas. Herein we report what are to our knowledge the first direct biocatalytic routes to BDO from renewable carbohydrate feedstocks, leading to a strain of Escherichia coli capable of producing 18 g l(-1) of this highly reduced, non-natural chemical. A pathway-identification algorithm elucidated multiple pathways for the biosynthesis of BDO from common metabolic intermediates. Guided by a genome-scale metabolic model, we engineered the E. coli host to enhance anaerobic operation of the oxidative tricarboxylic acid cycle, thereby generating reducing power to drive the BDO pathway. The organism produced BDO from glucose, xylose, sucrose and biomass-derived mixed sugar streams. This work demonstrates a systems-based metabolic engineering approach to strain design and development that can enable new bioprocesses for commodity chemicals that are not naturally produced by living cells.

A new class of chiral Cz-symmetric bis(phospho1ane) ligands has been prepared and used in rhodium-catalyzed asymmetric hydrogenation reactions. We describe a practical, one-pot procedure which utilizes enantiomerically pure 1,4-diol cyclic sulfates 4 for the preparation of a homochiral series of 1,2-bis(phospholano)ethanes 1 and 1,2-bis-(phospho1ano)benzenes (DuPHOS) 2. Cationic rhodium complexes bearing these new ligands behave as very efficient catalyst precursors for the asymmetric hydrogenation of a broad range of a-(N-acy1amino)acrylate (enamide) substrates 5. Significantly, a variety of unnatural and nonproteinaceous a-amino acid derivatives 6 were obtained directly with enantioselectivities approaching 100% ee when using the DuPHOS ligands 2. Substrate-to-catalyst ratios of 10 000 were routinely used, and ratios as high as 50 000 were demonstrated in these reactions. Details of the DuPHOS-Rh-catalyzed hydrogenations are discussed.Asymmetric phosphine ligands have played a dominant role in the development of novel transition-metal-catalyzed enantioselective syntheses.' Notwithstanding the high selectivities observed in certain applications using some of the more successful asymmetric phosphines such as DIPAMP,Z CHIRAPHOS,3 and BINAP: there are many reactions of interest where catalysts bearing these phosphines perform rather poorly in terms of efficiency and enantioselectivity. Such failure indicates the need for alternative asymmetric ligands and/or catalysts.Toward this goal, our research has been focused on the design of new chiral ligands for use in transition-metal-based asymmetric catalysis. We recently outlined our approach and described the synthesis of new electron-rich Cz-symmetric bis(phospho1ane) and C3-symmetric tris(phospho1ane) ligands-' These studies indicated the potential utility of Cz-symmetric 1 ,2-bis(phospholano)ethane ligands of type 1. The reported ligand preparation, however, was inefficient for cases other than the dimethylsubstituted diphospholane (Le., la, R = Me). We herein report details of an improved synthetic procedure that allows facile preparation of the homochiral series of Cz-symmetric 1,2-bis-(phospho1ano)ethanes 1 (BPE, R = Me, Et, Pr, and i-Pr). The evolutionary nature of our ligand design subsequently led us to prepare the analogous homochiral series of 1 ,2-bis(phospholano)benzene ligands 2 (DuPHOS, R = Me, Et, Pr, and i-Pr).sWe have found that the new ligands 1 and 2 afford efficient catalysts for the highly enantioselective hydr0genation5-~ and t Present address: hydrosilylation1° of various unsaturated substrates. In particular, enantioselectivities approaching 100% ee have been observed in the Rh-catalyzed hydrogenation of a wide range of a-(N-acy1amino)acrylates. Importantly, the high efficiency, selectivity, and substrate generality exhibited by these catalysts provide a practical route to a variety of enantiomerically pure unnatural and nonproteinaceous a-amino acid derivatives. The details of these hydrogenation studies are described herein. Results and Disc...

This Account outlines the preparation and application of a class of phosphine ligands based upon the trans-2,5-disubstituted phospholane moiety. The modular nature of these ligands has allowed facile variation of both phospholane substituent and backbone structure, thus providing access to a series of ligands. Bidentate bis(phospholane) ligands have been found to be very useful in asymmetric catalytic hydrogenation reactions. In particular, we highlight the versatility of highly efficient bis(phospholane)rhodium catalysts that allow enantioselective hydrogenation to produce a diverse range of compounds containing C-N, C-O, and C-C stereogenic centers.

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