Stereoselective intramolecular 1,3-dipolar nitrile oxide cycloaddition reaction of N-formyl-β-nitroamides

The stereoselective intramolecular nitrile oxide cycloaddition (INOC) reaction was achieved from N-formyl-β-nitroamides, which were prepared through the Michael addition of allylic formamides to nitroalkenes, and cis-pyrroroisoxazoles and trans-piperidinoisoxazoles were obtained in a stereoselective manner.     

A common strategy for the stereoselective synthesis of anhydrophytosphingosine pachastrissamine (jaspine B) and N,O,O,O-tetra-acetyl d-lyxo-phytosphingosine

The highly stereoselective Grignard addition on chiralimine 8 and opening of chiral epoxide 9 with Grignard reagent have been used as key steps in the stereoselective synthesis of cytotoxic anhydrophytosphingosine pachastrissamine (jaspine B) and N,O,O,O-tetra-acetyl d-lyxo-phytosphingosine.     

Artificial intelligence designed drug synthesis: One-pot preparation of trans β-lactams and application to cholesterol absorption inhibitor SCH 47949 synthesis

An artificial intelligence designed SCH 47949 synthesis is achieved in a stereoselective manner. The key step contains a stereoselective one-pot construction of the trans β-lactam framework via thermal electrocyclization. N-arylation of the β-lactam ring system and a series of functional group transformations synthesized SCH 47949 in a reasonable chemical yield.     

Stereoselective synthesis of (2S,3S)-3-hydroxy-2-phenylpiperidine from d-mannitol

A novel stereoselective synthesis of N-Boc-(2S,3S)-3-hydroxy-2-phenylpiperidine was achieved from d-mannitol involving the highly stereoselective addition of phenyl Grignard to an allyl imine (de >98%) and ring-closing metathesis (RCM) in the key steps.     

An efficient stereoselective synthesis of (+)-deoxoprosophylline

An efficient stereoselective synthesis of (+)-deoxoprosophylline from readily available p-anisaldehyde is described. Key steps in the synthesis include the stereoselective amination of anti-1,2-dibenzyl ether using chlorosulfonyl isocyanate, intermolecular olefination, and Pd-catalyzed intramolecular cyclization.     

Total synthesis of (−)-funebrine via Au-catalyzed regio- and stereoselective γ-butyrolactonization of allenylsilane

The stereoselective total synthesis of (−)-funebrine from 2-butyn-1-ol was described. The crucial steps in the synthesis involved the stereoselective enolate Claisen rearrangement of the (S)-α-acyloxy-α-alkynylsilane 8, the Au-catalyzed regio- and stereoselective lactonization of the allenylsilane 7, and the Paal-Knorr pyrrole condensation using an unsymmetrical 1,4-diketone 4b.     

New reactions of alkynes with ketones in superbasic media

The present work reviews new reactions of alkynes with ketones in the superbasic media MOH—DMSO (M = Na, K, Cs) and KOBu^t—DMSO: the stereoselective nucleophilic addition of deprotonated ketones to the triple bond to form the E-isomers of β,γ-enones; vinylation of tertiary acetylenic alcohols that formed in situ from acetylene and ketones; the direct synthesis of vinyl ethers of tertiary acetylenic alcohols from acetylene and ketones; the stereoselective synthesis of dispirocyclic ketals containing the Z-ethylene fragment from arylalkynes and two molecules of a cyclic ketone; the stereoselective cascade synthesis of hexahydroazulenones from two arylalkyne molecules and 2-alkylcyclohexanones; the stereoselective cascade assembly of 7-methylidene-6,8-dioxabicyclo[3.2.1]octanes from two acetylene molecules and two ketone molecules; the stereoselective cascade synthesis of 7-methylidene-6,8-dioxabicyclo[3.2.1]octanes from acetylenes and 1,5-diketones; and the three-component cascade reaction of acetylene, ketones, and oximes to afford 4-methylidene-3-oxa-1-azabicyclo-[3.1.0]hexanes.     

Novel construction of the brassinolide side chain

A stereoselective synthesis of brassinolide, which involves construction of the side chain by a highly stereoselective aldol reaction between 20S-6β-methoxy-3α,5-cyclo-5α-pregnane-20-carboxaldehyde 2 and ketone 3 or 4 catalyzed by l-proline, is described.     

A stereoselective total synthesis of (−)-seychellene

A stereoselective total synthesis of the tricyclic sesquiterpene (−)-seychellene, starting from (R)-carvone via (R)-3-methylcarvone has been accomplished, employing a combination of intermolecular Michael addition-intramolecular Michael addition sequence, a stereoselective hydrogenation, and an intramolecular alkylation reaction.     

Stereoselective synthesis of substituted dienes by the double ortho ester Claisen rearrangement

This letter shows the highly stereoselective synthesis of substituted (E)-1,3-dienes from substituted propargylic diols via the double ortho ester Claisen rearrangement. The cyclohexyl-substituted diene undergoes thermal Diels-Alder cycloaddition with maleic anhydride to produce the corresponding bicyclic diester in highly stereoselective manner.     

A concise and stereoselective synthesis of the brassinolide and related compounds’ side chains

A stereoselective synthesis of brassinolide, which involves construction of the side chain by highly stereoselective aldol reaction of 20S-6β-methoxy-3α,5-cyclo-5α-pregnane-20-carboxadehyde 5 with the anion of α-silyloxy ketone 6 is described.     

Stereoselective synthesis and anti-HCV activity of conformationally restricted 2′-C-substituted carbanucleosides

Conformationally restricted 2′-C-azido-, hydroxy- and fluoromethyl-carbanucleosides 4b–f were efficiently synthesized via the stereoselective conversion of ketone 7 to epoxide 14, followed by the stereoselective opening of the epoxide with nucleophiles (OAc, N₃, and F), while the corresponding 2′-C-methyl-carbanucleoside 4a was synthesized via the stereoselective Grignard reaction of ketone 7 with methylmagnesium iodide as a key step. All the final nucleosides 4a–f were assayed for anti-HCV activity, but showed neither significant anti-HCV activity nor cytotoxicity in a cell-based replicon assay.     

Stereoselective synthesis and Lewis acid mediated functionalization of novel 3-methylthio-β-lactams

A proficient etiquette for the stereoselective synthesis of novel 3-methylthio-β-lactams and their Lewis acid mediated functionalization is described. Treatment of 2-methylthioethanoic acid and appropriate imines in the Staudinger reaction leads to the stereocontrolled synthesis of novel trans-3-methylthio-β-lactams in excellent yields. cis-3-Chloro-3-methylthio-β-lactams, obtained from stereoselective chlorination of trans-3-methylthio-β-lactams using N-chlorosuccinimide (NCS) and AIBN, were subjected to Lewis acid (TiCl₄ or SnCl₄) mediated functionalization using various active aromatic, heterocyclic and aliphatic compounds (nucleophiles). This reaction provides an easy access to novel, stereoselective cis-3-monosubstituted-3-methylthio-β-lactams, which further undergo smooth desulfurization with Raney-nickel to afford C-3 cis- and trans-monosubstituted-β-lactams. The cis or trans configuration of the hydrogen/chloro/nucleophile substituent at C-3 was assigned with respect to C4–H.     

Synthesis of a lactone natural product found in Greek tobacco

A short and stereoselective synthesis of (3R^∗,4R^∗,7R^∗)-3,7-epoxy-4,8-dimethyl-8-nonen-4-olide, a natural product isolated from cured tobacco leaves, has been completed in six steps and 22% overall yield. A samarium(II) iodide mediated reductive cyclisation has been used to construct the functionalised tetrahydropyranol core and subsequent sequential stereoselective addition of methyllithium and lactonisation furnished the natural product.     

Intermolecular cycloaddition of nonstabilized azomethine ylides generated from 1,3-thiazolidine-4-carboxylic acids: synthesis of 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazoles

The 1,3-dipolar cycloaddition of dimethyl acetylenedicarboxylate with nonstabilized azomethine ylides, generated via the decarboxylative condensation of 1,3-thiazolidine-4-carboxylic acids with aldehydes, afforded 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazole derivatives. 2-Substituted-1,3-thiazolidine-4-carboxylic acids led to the stereoselective formation of 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazoles. Quantum-chemistry calculations were carried out allowing the rationalization of the observed stereoselective formation of the anti-dipole.     

A highly stereoselective total synthesis of (±)-isoalantolactone

(±)-Isoalantolactone (1) has been synthesized by a highly stereoselective route from the versatile bicyclic ketone, trans-5-methylene-9-methyl-2-decalone 2. Three major points in the synthesis involve (a) introduction of the acetic acid side chain; (b) stereoselective reduction of the ketone function yielding cis-lactone 6; and (c) introduction of the α-methylene group onto the butyrolactone ring.     

Synthetic studies on cytotoxic macrolides cruentarens A and B: stereoselective synthesis of the C8–C19 segment of cruentarens A and B

A stereoselective synthesis of the C₈–C₁₉ segment of cruentarens A and B, cytotoxic natural products, has been accomplished. The key steps involve a stereoselective radical cyclization, stereospecific methylation of a γ, δ-epoxy acrylate, nucleophilic epoxide ring opening and a cis-Wittig olefination.     

Stereoselective synthesis of both enantiomers of trans-2-(diphenylmethylideneamino)cyclopropanecarboxylic acid using a chiral pool approach and their incorporation in dipeptides

The stereoselective synthesis of (1R,2R)- and (1S,2S)-trans-2-(diphenylmethylideneamino)cyclopropanecarboxylic acid has been accomplished in six steps starting from (2S)- and (2R)-β-benzyl N-(tert-butoxycarbonyl)aspartate, respectively. The key-step in the reaction sequence is a stereoselective base-induced ring closure with a good trans diastereoselectivity. These novel trans-β-ACC derivatives could be incorporated in dipeptides employing a standard peptide coupling technique.     

Stereoselective syntheses of tri- and tetrapeptide analogues by dynamic resolution of α-halo amides in nucleophilic substitution

Dynamic resolution of α-bromo and α-chloro acetamides in nucleophilic substitution with amine nucleophiles in the presence of TBAI has been investigated for stereoselective syntheses of tri- and tetrapeptide analogues. Mechanistic investigations suggest that primary pathway of the asymmetric induction is a dynamic kinetic resolution and real intermediate for the substitution is α-iodo acetamides. Also, application of this mild and simple methodology to stereoselective preparations of N-carboxyalkyl, N-aminoalkyl and N-hydroxyalkyl peptide analogues is demonstrated.