Sang-gi Lee

Biosynthesis of the Allylmalonyl-CoA Extender Unit for the FK506 Polyketide Synthase Proceeds through a Dedicated Polyketide Synthase and Facilitates the Mutasynthesis of Analogues

The allyl moiety of the immunosuppressive agent FK506 is structurally unique among polyketides and critical for its potent biological activity. Here, we detail the biosynthetic pathway to allylmalonyl-coenzyme A (CoA), from which the FK506 allyl group is derived, based on a comprehensive chemical, biochemical, and genetic interrogation of three FK506 gene clusters. A discrete polyketide synthase (PKS) with noncanonical domain architecture presumably in coordination with the fatty acid synthase pathway of the host catalyzes a multistep enzymatic reaction to allylmalonyl-CoA via trans-2-pentenyl-acyl carrier protein. Characterization of this discrete pathway facilitated the engineered biosynthesis of novel allyl group-modified FK506 analogues, 36-fluoro-FK520 and 36-methyl-FK506, the latter of which exhibits improved neurite outgrowth activity. This unique feature of FK506 biosynthesis, in which a dedicated PKS provides an atypical extender unit for the main modular PKS, illuminates a new strategy for the combinatorial biosynthesis of designer macrolide scaffolds as well as FK506 analogues.

Catalytic asymmetric hydrogenation in a room temperature ionic liquid using chiral Rh-complex of ionic liquid grafted 1,4-bisphosphine ligandElectronic supplementary information (ESI) available: experimental details. See http://www.rsc.org/suppdata/cc/b3/b309304b/

Introduction of imidazolium ionic liquid pattern to the catalyst not only avoided catalyst leaching but also increased the stability of catalyst in ionic liquid, and thus, the Rh-complex of 1,4-bisphosphine bearing two imidazolium salt moieties was successfully immobilized in an ionic liquid and reused several times for the hydrogenation of an enamide without significant loss of catalytic efficiency.

DMF as a source of oxygen and aminomethine: stereoselective 1,2-insertion of rhodium(II) azavinyl carbenes into the C═O bond of formamides for the synthesis of cis-diamino enones.

A new catalytic reaction in which all the atoms of a formamide are incorporated into the product through a formal stereoselective 1,2-insertion of rhodium(II) azavinyl carbenes, generated in situ from readily available N-sulfonylated 1,2,3-triazoles, into the C═O bond of DMF and other N,N-disubstituted formamides to afford cis-diamino enones is described.

Efficient and practical polymeric catalysts for heterogeneous asymmetric dihydroxylation of olefins

Abstract High enantioselectivity (>99% ee) and reactivity in heterogeneous catalytic asymmetric dihydroxylation (AD) of olefins have been achieved using new polymeric cinchona alkaloids containing 1,4-bis(9- O -quininyl)phthalazine ((QN) 2 -PHAL), which can be synthesized more economically than their homogeneous analogue, 1,4-bis(9- O -dihydroquininyl)phthalazine ((DHQ) 2 -PHAL).

Tandem one-pot synthesis of polysubstituted pyridines using the Blaise reaction intermediate and 1,3-enynes.

A tandem one-pot method for the construction of a pyridine moiety with selective control of substitution patterns has been developed through the sequential reactions of nitrile with a Reformatsky reagent and 1,3-enyne involving regio- and chemoselective addition of the Blaise reaction intermediate to 1,3-enyne, followed by isomerization, cyclization, and an aromatization cascade.

Metallic Lewis acids-catalyzed acetylation of alcohols with acetic anhydride and acetic acid in ionic liquids: study on reactivity and reusability of the catalysts

Abstract The catalytic activity and reusability of the metallic Lewis acids, Cu(OTf)2, Yb(OTf)3, Sc(OTf)3, In(OTf)3, HfCl4·(THF)2 and InCl3, for acetylation of alcohols with acetic anhydride and acetic acid has been examined in environmentally benign room temperature ionic liquids, [bmim][X] (bmim=1-n-butyl-3-methylimidazolium, X=PF6, BF4, SbF6). All of the catalysts effectively catalyzed the acetylation with acetic anhydride in an ionic liquid, [bmim][PF6]. In direct acetylation with acetic acid, Yb(OTf)3, Sc(OTf)3 and InCl3 showed excellent catalytic activity in the [bmim][PF6] ionic liquid and were reasonably recycled.

Palladium-catalyzed intramolecular trapping of the Blaise reaction intermediate for tandem one-pot synthesis of indole derivatives.

Palladium-catalyzed intramolecular N-arylative and N-alkylative/N-arylative trappings of the Blaise reaction intermediates could be a new route to construct the indole moiety in a tandem one-pot manner from nitriles.

New C2-symmetric chiral ketones for catalytic asymmetric epoxidation of unfunctionalized olefins

Abstract Using new C 2 -symmetric chiral ketones 4 and 6 as precursors for chiral dioxiranes generated in situ , the asymmetric epoxidation of olefins has been achieved in moderate ee.

Thermal behaviors of ionic liquids under microwave irradiation and their application on microwave-assisted catalytic Beckmann rearrangement of ketoximes

Abstract Microwave-assisted Beckmann rearrangements of ketoximes in room temperature ionic liquids have been accomplished successfully using only 5 mol% of H2SO4 as a catalyst.

Osmium tetroxide–(QN)2PHAL in an ionic liquid: a highly efficient and recyclable catalyst system for asymmetric dihydroxylation of olefins

In Os-catalysed asymmetric dihydroxylation using NMO as a co-oxidant, the combination of an ionic liquid and the new bis-cinchona alkaloid 2 generated in situ from (QN)2PHAL during reaction provided a simple and practical approach to the recycling of both catalytic components (osmium tetraoxide and chiral ligand).