16668-00-1

Upstream product

• 7511-40-2 (2S,3S,4S,5R,6R)-2-methoxy-6-((trityloxy)methyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate 
• 20231-36-1 methyl 6-O-trityl-α-D-mannopyranoside 
• 38982-56-8 methyl 2,3,4-tri-O-acetyl-6-O-trityl-α-D-galactopyranoside 
• 290359-93-2 (2R,3R,4S,5R,6S)-2-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-6-methoxy-tetrahydro-pyran-3,4,5-triol 
• 67-56-1 methanol 
• 108-24-7 acetic anhydride 
• 67298-15-1 dapiramicin A 
• 51023-63-3 methyl-α,β-D-mannopyranoside 
• 181480-80-8 6-O-tert-butyldimethylsilanyl-1-O-methyl-α-D-galactopyranoside 
• 594841-23-3 Acetic acid (2R,3S,4S,5R,6S)-3,5-diacetoxy-2-(tert-butyl-dimethyl-silanyloxymethyl)-6-methoxy-tetrahydro-pyran-4-yl ester 
• 5019-22-7 methyl 2,3,4,6-tetra-O-acetyl-α-D-galactopyranoside 
• 18311-26-7 methyl 6-O-triphenylmethyl-α-D-galactopyranoside 
• 3396-99-4 methyl α-D-galactopyranoside 
• 74247-81-7 6-O-tert-butyldimethylsilanyl-1-O-methyl-α-D-mannopyranoside 

Downstream Products

• 1372204-42-6 methyl 6-deoxy-6-(4-(5-trifluoromethyl-2(1H)-pyridone-1-yl)-anilino)-α-D-mannopyranoside 
• 1372204-43-7 methyl 6-deoxy-6-(3-chloro-4-(5-trifluoromethyl-2(1H)-pyridone-1-yl)-anilino)-α-D-mannopyranoside 
• 1372204-44-8 methyl 6-deoxy-6-(3-(5-trifluoromethyl-2(1H)-pyridone-1-yl-methyl)-anilino)-α-D-mannopyranoside 
• 1372204-46-0 methyl 6-deoxy-6-(4-(5-trifluoromethyl-2(1H)-pyridone-1-yl-methyl)-anilino)-α-D-mannopyranoside 
• 1372204-48-2 methyl 6-deoxy-6-(2-(5-trifluoromethyl-2(1H)-pyridone-1-yl-methyl)-anilino)-α-D-mannopyranoside 
• 7511-38-8 methyl 2,3,4-tri-O-acetyl-6-deoxy-6-iodo-β-D-glucopyranoside 

Relevant academic research and scientific papers

One-pot oxidation-hydrocyanation sequence coupled to lipase-catalyzed diastereoresolution in the chemoenzymatic synthesis of sugar cyanohydrin esters

A three-step, one-pot synthesis and diastereoresolution sequence is described in anhydrous toluene starting from methyl α-D-2,3,4-tri-O- acetylgalacto- (1a), -manno- (1b) and -glucopyranosides (1c). The reaction sequence, including consecutive transformations through the aldehyde [PhI(OAc)2, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)] and cyanohydrin [basic resin or (R)-oxynitrilase] into the (6R)-cyanohydrin ester (lipase) is shown to proceed in a one-pot cascade, except that the basic resin (when used) should be removed before the addition of the enzymatic acylation reagents. We have shown that the effective transformation of 1a (75 % reaction yield) through labile intermediates gives the stable (6R)-cyanohydrin butanoate (85 % de). Further diastereomeric purification by chromatography is possible, although the product is already of high diastereopurity. (6R)-Cyanohydrin esters are obtained through acylation with Burkholderia cepacia lipase. The (6S)-ester (de 99 %) is produced by Candida rugosa lipase when the sequence is started from 1c whereas the other sugar derivatives are less suited to the reaction with lipase. Copyright

Chemoenzymatic synthesis of neoglycoproteins driven by the assessment of protein surface reactivity

In this paper a series of 2-iminomethoxyethyl mannose-based mono- and disaccharides have been synthesized by a chemoenzymatic approach and used in coupling reactions with ε-amino groups of lysine residues in a model protein (ribonuclease A, RNase A) to give semisynthetic neoglycoconjugates. In order to study the influence of structure of the glycans on the conjugation outcomes, an accurate characterization of the prepared neoglycoproteins was performed by a combination of ESI-MS and LC-MS analytical methods. The analyses of the chymotryptic digests of the all neoglycoconjugates revealed six Lys-glycosylation sites with a the following order of lysine reactivity: Lys 1 Lys 91 ? Lys 31 > Lys 61 ? Lys 66. A computational analysis of the reactivity of each lysine residue has been also carried out considering several parameters (amino acids surface exposure and pKa, protein flexibility). The in silico evaluation seems to confirm the order in lysine reactivity resulting from proteomic analysis.

FORMATION OF 6-DEOXY-6-IODOHEXOPYRANOSIDES AS SUBSTRATES FOR THE HEX-5-ENOSE DEGRADATION

The synthesis of 6-deoxy-6-iodohexopyranosides as potential substrates for the hex-5-enose degradation has been examined for a range of mono-, di-, and poly-saccharide derivatives.It is shown that (1) unsubstituted D-glucopyranosides undergo selective, primary iodination without unwanted side-reactions; (2) primary iodination of D-galactopyranosides is accompanied by 3,6-anhydride formation, so that the desired reaction is only possible with protection of secondary hydroxyl groups; and (3) the extent of iodination in substrates of higher molecular weight is conveniently determined by reaction of acetylated (or methylated) derivatives with tributylstannane, followed by analysis of the resulting 6-deoxyhexopyranosides.The formation of 6-deoxy-6-iodohexopyranosyl residues in otherwise methylated plant galactomannans proceeds satisfactorily for (terminal) α-D-galactopyranosyl groups but incompletely for unbranched β-D-mannopyranosyl residues.

Lipases in the regioselective preparation of glyceric acid esters of methyl glycosides

The lipase-catalyzed regioselective acylation of methyl α-D-galacto-, -gluco- and -mannopyranosides with isopropylidene-protected (R)- and (S)-glyceric acid methyl esters in organic solvents is presented. Factors affecting the formation of the 6-O-mono- and 2,6-O-diacylated products are examined and preparative-scale reactions are detailed. In addition, studies on partially protected methyl α-D-galactopyranosides are presented, with the 3,4-O-isopropylidene protected compound leading exclusively to the formation of the 6-O-monoacylated product even at high substrate concentrations. Application of acidic resin in methanol allows removal of the isopropylidene protection groups without disturbing the ester bond at C-6. Copyright

Discriminating non-ylidic carbon-sulfur bond cleavages of sulfonium ylides for alkylation and arylation reactions

A sulfonium ylide participated alkylation and arylation under transition-metal free conditions is described. The disparate reaction pattern allowed the separate activation of non-ylidic S-alkyl and S-aryl bond. Under acidic conditions, sulfonium ylides serve as alkyl cation precursors which facilitate the alkylations. While under alkaline conditions, cleavage of non-ylidic S-aryl bond produces O-arylated compounds efficiently. The robustness of the protocols were established by the excellent compatibility of wide variety of substrates including carbohydrates.

Zirconium-Catalyzed Hydroalumination of C=O Bonds: Site-Selective De- O-acetylation of Peracetylated Compounds and Mechanistic Insights

An unprecedented hydroalumination of C = O bonds catalyzed by zirconocene dichloride is reported herein and applied to the site-selective deprotection of peracetylated functional substrates. A mixed metal hydride, with 1:1 zirconium/aluminum stoichiometry

Regio- A nd chemoselective deprotection of primary acetates by zirconium hydrides

A combination of DIBAL-H and Cp2ZrCl2 is shown to promote the regioselective cleavage of primary acetates on a broad scope of substrates, ranging from carbohydrates to terpene derivatives, with a high tolerance toward protecting groups and numerous functionalities found in natural products and bioactive compounds. Apart from providing highly valuable building blocks in only two steps from biosourced raw materials, this selective de-O-acetylation should also be strongly helpful to solve selectivity issues in organic synthesis.

MACROCYCLIC MCL-1 INHIBITORS AND METHODS OF USE

The present disclosure provides for compounds of Formula (I) wherein A2, A3, A4, A6, A7, A8, A15, RA, R5, R9, R10A, R10B, R11, R12, R13, R14, R16, W, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including cancer. Also provided are pharmaceutical compositions comprising compounds of Formula (I).

Visible-Light-Mediated, Chemo- and Stereoselective Radical Process for the Synthesis of C-Glycoamino Acids

An approach for efficient synthesis of C-glycosyl amino acids is described. Different from typical photoredox-catalyzed reactions of imines, the new process follows a pathway in which α-imino esters serve as electrophiles in chemoselective addition reactions with nucleophilic glycosyl radicals. The process is highlighted by the mild nature of the reaction conditions, the highly stereoselectivity attending C-C bond formation, and its applicability to C-glycosylations using both armed and disarmed pentose and hexose derivatives.

NEW HYDROXYACID DERIVATIVES, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

Compounds of formula (I): wherein R1, R2, R3, R4, R5, R6, R7, R8, R14, A and n are as defined in the description. Medicaments.