Jacek Mlynarski

Catalysts Based on Amino Acids for Asymmetric Reactions in Water

Asymmetric organometallic and organocatalytic processes in aqueous systems are currently of great interest. A few years ago, only a few practitioners studied the subject; now organic reactions in water have become one of the most exciting research areas. The quest to identify water-compatible catalysts has evoked an intense search for new possibilities. Following natures lead, the application of amino acids as sources of chiral information seems particularly promising for aqueous systems. Herein we provide an overview of very recent advances in the area of asymmetric catalysis in water with amino acids and their derivatives as effective catalysts or essential components of catalysts.

Direct Asymmetric Aldol Reactions Inspired by Two Types of Natural Aldolases: Water-Compatible Organocatalysts and ZnII Complexes

In this article the utility of water-compatible amino-acid-based catalysts was explored in the development of diastereo- and enantioselective direct aldol reactions of a broad range of substrates. Chiral C(2)-symmetrical proline- and valine-based amides and their Zn(II) complexes were designed for use as efficient and flexible chiral catalysts for enantioselective aldol reactions in water, on water, and in the presence of water. The presence of 5 mol % of the prolinamide-based catalyst affords asymmetric intermolecular aldol reactions between unmodified ketones and various aldehydes to give anti products with excellent enantioselectivities. We also demonstrate aldol reactions of more demanding substrates with high affinity to water (i.e., acetone and formaldehyde). Newly designed serine-based organocatalyst promoted aldol reaction of hydroxyacetone leading to syn-diols. For presented catalytic systems organic solvent-free conditions are also acceptable, making the elaborated methodology interesting from a green chemistry perspectives.

Efficient “on water” organocatalytic protocol for the synthesis of optically pure warfarin anticoagulant

The present development leads to an efficient protocol for the “on water” formation of one of the most widely used anticoagulants warfarin: the presented scalable and environmentally friendly organocatalytic approach affords the target drug in optically pure form.

Amine-Catalyzed Direct Aldol Reactions of Hydroxy- and Dihydroxyacetone: Biomimetic Synthesis of Carbohydrates

This article presents comprehensive studies on the application of primary, secondary, and tertiary amines as efficient organocatalysts for the de novo synthesis of ketoses and deoxyketoses. Mimicking the actions of aldolase enzymes, the synthesis of selected carbohydrates was accomplished in aqueous media by using proline- and serine-based organocatalysts. The presented methodology also provides direct access to unnatural L-carbohydrates from the (S)-glyceraldehyde precursor. Determination of the absolute configuration of all obtained sugars was feasible using a methodology consisting of concerted ECD and VCD spectroscopy.

The first synthesis of the ketene dithioacetals from sugar lactones: a convenient access to 3-ulosonic acids

Abstract Isomeric 2-deoxy aldonolactones undergo Horner-Emmons reactions with 2-[bis(2,2,2-trifluoroethoxy)phosphoryl]1,3-dithiane, to give the corresponding ketene dithioacetals, which are the key intermediates in the synthesis of 3-deoxy-2-keto-aldonic acids.

Synthetic approach to 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) α-disaccharides via a ketene dithioacetal

Abstract A unique strategy for the synthesis of Kdo α-disaccharides based on the ketene dithioacetal 4 (precursor of Kdo) as a ‘glycosyl donor’ has been developed. Direct, fully stereoselective addition of 6-, 7-, or 8-OH unprotected sugar units to the exo -anomeric double bond in 4 , promoted by trimethylsilyl triflate, led to the corresponding O -disaccharides 12 with the dithioacetal residue intact. Subsequent hydrolysis of the later afforded the title compounds in high yields.

A NOVEL CHEMICAL SYNTHESIS OF A 3-DEOXY-D-ARABINO-HEPTULOSONIC ACID 7-PHOSPHATE (DAHP) DERIVATIVE AND ITS 2-DEOXY ANALOGUE

Abstract Using 2,3,4,6-tetra- O -acetyl- β - d -glucopyranosyl cyanide as a precursor, methyl (methyl 3-deoxy-α- d - arabino -hept-2-ulopyranosid)onate ( 6 ) and its 2-deoxy analogue ( 10 ) were prepared. The synthesis involved an elimination of one molecule of acetic acid from C-2–C-3 and transformation of the CN group into COOMe, followed by methoxymercuration with subsequent reductive removal of the mercuri residue to give 6 or hydrogenation of the double bond to give 10 . Phosphorylation of the 7-OH group led to the title compounds.

Aggregation-Induced Resonance Raman Optical Activity (AIRROA): A New Mechanism for Chirality Enhancement

Raman optical activity (ROA) spectroscopy is hampered by low sensitivity, with limited possibilities for enhancing the signal. In the present study, we report a new mechanism whereby chirality is enhanced using the resonance resulting from supramolecular aggregation. We have named this mechanism aggregation-induced resonance Raman optical activity (AIRROA). As an example, we study J-aggregates of astaxanthin (AXT), which show strong absorption of circularly polarized light in the range of ROA excitation. The implications of aggregation-induced signal enhancement for chiroptical spectroscopy are discussed.

Recent Advances in the Chemistry of Bioactive 3-Deoxy-Ulosonic Acids

Abstract This article describes recent developments in the chemistry of an important family of complex monosaccharides which have diverse structures and participate in a wide range of biological processes. For example: 3-deoxy- d - manno -2-octulosonic acid (KDO) is a key component of the lipopolysaccharides (LPS) of Gramm-negative bacteria, 3-deoxy- d - arabino -2-heptulosonic acid (DAH) is a key intermediate in the biosynthesis of aromatic amino acids in bacteria and plants. A number of their syntheses that were achieved by homologation reactions of the natural carbohydrate units using enzymatic or chemical methods, as well as by total synthetic approaches are here included. Special emphasis is placed on new methodologies and their correlation with the biosynthetic pathway of the corresponding ulosonic acids. This chapter is not intended to cover all available literature, since other review articles have been published. It tries to demonstrate the real contribution, showing that the development of general and efficient strategies for the construction of these important compounds still remains as significant.

Synthetic routes to methyl 3-deoxy-aldulosonic acid methyl esters and their 2-deoxy isomers based on the Horner-Emmons and Peterson reaction of sugar lactones

Abstract The two reagents: 2-trimethylsilyl- and 2-[bis(2,2,2-trifluoroethoxy)phosphoryl]-1,3-dithianes were engaged in the construction of appropriate ketene thioacetals from the isomeric 2-deoxy-hexono-1,5-lactones via Horner-Emmons or Peterson reaction. A comparison of the results shows that the second reagent is more promising, as it forms the desired ketene thioacetals as sole products. The latter were directly transformed stereoselectively into the title α ulosonates in an oxidative hydrolysis reaction, using NBS/MeOH in CH2Cl2. A construction of the methyl 2-deoxy-ulosonates involved a preceding hydrogenation of the double bond by LiBH4-TMSCl species, and subsequent hydrolysis with NBS in aqueous THF medium.