Asymmetric synthesis of the central tryptophan residue of stephanotic acid

The C-6 substituted tryptophan di- and tri-peptides and , representing the tryptophan core of stephanotic acid, have been synthesized, the key steps being the formation of the phosphono-di- and tri-peptides and by a highly chemoselective rhodium(II) catalyzed carbene N-H insertion reaction, their subsequent Horner-Wadsworth-Emmons reactions with N-Boc-6-bromoindole-3-carboxaldehyde, and the rhodium(I) catalyzed asymmetric hydrogenation of the resulting dehydro di- and tri-peptides.     

Asymmetric synthesis of highly substituted gamma-amino acids from allyltitanium sulfoximines

[structure: see text]. Asymmetric syntheses of the highly substituted protected gamma-amino acids 10a, 10b, 18, and 21 have been developed starting from the allyltitanium sulfoximines V and VI, respectively, and furan-2-carbaldehyde.     

Asymmetric synthesis of highly functionalized tetrahydrothiophenes by organocatalytic domino reactions

A simple approach for the formation of optically active highly functionalized tetrahydrothiophenes, which might find important use in biochemistry, pharmaceutical science, and nanoscience is presented. Development of new organocatalytic Michael-aldol domino reactions is outlined, and with the appropriate choice of additives it is possible to control the regioselectivity of these domino reactions, yielding diastereomerically pure (tetrahydrothiophen-2-yl)phenyl methanones or tetrahydrothiophene carbaldehydes in good yields and with excellent enantioselectivities up to 96% ee. The stereochemical outcome of these reactions is investigated, and the mechanism of these organocatalytic domino processes is presented.     

Asymmetric synthesis of highly functionalized tyrosine derivatives for the construction of bistetrahydroisoquinoline alkaloids

A novel and facile synthesis of l-5-hydroxy-2,4-methoxy-3-methylphenylalanine derivatives, which are the key coupling partners for the asymmetric total synthesis of natural bistetrahydroisoquinoline alkaloids, is realized starting from l-tyrosine with 17% overall yield. The synthesis has been carried out on a multigram scale featuring the following key steps: (a) transformation of phenol to dihydroquinone via salcomine-catalyzed oxidation followed by zinc-acetic acid reduction; (b) single TBS-protection of dihydroquinone; (c) Mitsunobu methylation of the newly generated phenolic hydroxyl group.     

Asymmetric synthesis of the highly potent anti-metastatic prostacyclin analogue cicaprost and its isomer isocicaprost

An asymmetric synthesis of the anti-metastatic prostacyclin analogue cicaprost and a formal one of its isomer isocicaprost by a new route are described. A key step of these syntheses is the coupling of a chiral bicyclic C6-C14 ethynyl building block with a chiral C15-C21 omega-side chain amide building block with formation of the C14-C15 bond of the target molecules. A highly stereoselective reduction of the thereby obtained C6-C21 intermediate carrying a carbonyl group at C15 of the side chain was accomplished by the chiral oxazaborolidine method. The chiral phosphono acetate method was used for the highly stereoselective attachment of the alpha-side chain to the bicyclic C6-C21 intermediate carrying a carbonyl group at C6. Asymmetric syntheses of the bicyclic C6-C14 ethynyl building blocks were carried out starting from achiral bicyclic C6-C12 ketones by using the chiral lithium amide method. In the course of these syntheses, a new method for the introduction of an ethynyl group at the alpha-position of the carbonyl group of a ketone with formation of the corresponding homopropargylic alcohol was devised. Its key steps are an aldol reaction of the corresponding silyl enol ether with chloral and the elimination of a trichlorocarbinol derivative with formation of the ethynyl group. In addition, a new aldehyde to terminal alkyne transformation has been realized. Its key steps are the conversion of an aldehyde to the corresponding 1-alkenyl dimethylaminosulfoxonium salt and the elimination of the latter with a strong base. Two basically different routes have been followed for the synthesis of the enantiomerically pure C15-C21 omega-side chain amide building block. The first is based on the chiral oxazolidinone method and features a highly stereoselective alkylation of (4R)-N-acetyl-4-benzyloxazolidin-2-one, and the second encompasses a malonate synthesis of the racemic amide and its efficient preparative scale resolution by HPLC on a chiral stationary phase containing column.     

Asymmetric allylation. An effective strategy for the convergent synthesis of highly functionalized homoallylic alcohols

A survey of stereoselective syntheses of highly-functionalized homoallylic alcohols is described via asymmetric allylation. Initial transmetalation from an allylic stannane to a C-2 symmetric chiral borane controller is followed by low temperature addition to aldehydes efficiently effecting convergent strategies to complex targets.     

Asymmetric synthesis of highly substituted beta-nitro alcohols and enantiomerically enriched 4,4,5-trisubstituted oxazolidinones

It is demonstrated that alpha,alpha-disubstituted-alpha-nitroketones are reduced to the corresponding trisubstituted nitro alcohols in good to excellent yield and enantiomeric excess by borane-dimethyl sulfide in the presence of a chiral oxazaborolidine catalyst. Reduction of the nitro alcohols to the corresponding amino alcohols and their subsequent conversion to enantiomerically enriched 4,4,5-trisubstituted oxazoldinones is also reported.     

Solid-phase synthesis of bis-2-imidazolidinethiones from resin-bound tripeptides

The exhaustive reduction of resin-bound tripeptides with borane afforded three secondary amines and one primary amine. The treatment of the solid-support polyamines with thiocarbonyldiimidazole afforded, following cleavage of the solid support, the corresponding bis-cyclic thiourea in good purity and yield.     

Asymmetric epoxidation of cis-alkenes mediated by iminium salts: highly enantioselective synthesis of levcromakalim

[reaction: see text] A range of cis-substituted olefins has been epoxidized with a new dihydroisoquinolinium salt catalyst, using tetraphenylphosphonium monoperoxysulfate as the stoichiometric oxidant, giving ee's of up to 97%. The reaction has been used as the key step in an enantioselective synthesis of the antihypertensive agent levcromakalim.     

Asymmetric hydrogenation of tryptophan precursors catalyzed by rhodium-DIOP complexes

Z-2-benzamido(acetamido)-3-(3-indolyl)-2-propenoic acids were hydrogenated with neutral and cationic rhodium(I) complexes containing the chiral diphosphine (–) or (+)–2,3-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)-butane [(–) or (+)–DIOP].

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Z-2- ()-3-(3-)-2- () (I), (–) (+)-2,3--2,3--1,4- ()-.

     

Asymmetric synthesis of 1,2-disubstituted cycloalkanecarboxaldehydes. procedures for the highly stereoselective preparation of cis- and trans-isomer

Procedures for the asymmetric synthesis of 1,2-disubstituted cycloalkanecarboxaldehydes ($\text{7}$) having assymetric tertiary and quaternary carbon atoms in vicinal positions from the corresponding cycloalkenecarboxaldehydes ($\text{2}$) in high diastereomeric and enantiomeric purities are described.     

A concise synthesis of the naphthalene portion of purpuromycin

A concise synthesis of naphthalene compounds for incorporation into a synthetic sequence for the rubromycin family of natural products is presented. These highly substituted naphthalenes are generated in seven and nine steps, respectively, from 2,4,5-trimethoxybenzaldehyde. Three ring-forming methods were explored and the controlled oxygenation of different positions was investigated to yield differentially substituted/protected systems. Key steps to the final products include a Stobbe condensation to form the ring system and a novel series of regioselective oxidations to introduce the required oxygen functionality. These naphthalene products incorporate orthogonal protecting groups and are suitable for combination with a variety of coupling partners.     

Asymmetric synthesis of furofurans

Furofurans are one of the largest sub-types of classical lignans which have been found to possess a broad range of important biological activities. Tremendous efforts have been directed to develop synthetic methodologies for the synthesis of furofurans, especially in a stereoselective manner, due to their interesting bioactivities associated with the structural and stereochemical complexity. This article summarizes the reports on asymmetric synthesis of furofurans disclosed during the period of 2004–2017.     

Asymmetric synthesis of triepoxyzerumbol

The achiral sesquiterpene zerumbone 1, which is readily available from wild ginger, has a unique functionality and reactivity making it a convenient starting material for its conversion into useful compounds, such as paclitaxel. Optically active triepoxyzerumbol (−)-3 and its acetate (+)-4 were synthesized by lipase-catalyzed enantioselective transesterification of racemic 3. Under optimized conditions, a lipase from Alcaligenes sp. (Meito QL) catalyzed the reaction of racemic 3 with isopropenyl acetate in THF at 35 °C to afford (1S)-3 and (1R)-4 with an E-value of 79. The absolute configuration of (1R)-4 was determined by single crystal X-ray diffraction of its ester with a chlorine atom using the anomalous dispersion effect.     

非甾体消炎药萘普生不对称合成研究

萘普生[(S)-(+)-S-(6'-甲氧基-2'-萘基)丙酸]是一种非常重要的非甾体消炎镇痛药。以(2R,3R)-酒石酸二甲酯为手性辅助剂,2-甲氧基萘经溴代、丙酰化、缩酮化、不对称溴化、水解、立体专一性重排和催化氢转移氢解等反应合成了光学活性萘普生,化学收率44%。制备的萘普生的光学纯度([α]~D^2^5=+63.5ⅲ)符合中华人民共和国药典(1995年版)的要求。     

Asymmetric synthesis of ageliferin

We describe herein an asymmetric synthesis of ageliferin. A Mn(III)-mediated oxidative radical cyclization reaction was used as the key step to construct the core skeleton of this pyrrole-imidazole dimer. This approach resembles the biogenic [4 + 2] dimerization in an intramolecular fashion.     

Asymmetric synthesis of fagomine

We report an asymmetric synthesis of the alkaloid fagomine, which is an inhibitor of mammalian α-glucosidase and β-galactosidase, by means of Sharpless asymmetric dihydroxylation and Pd(II)-catalyzed cyclization, starting from 3-(t-butoxylcarbonylamino)propanol.