Asymmetric synthesis of (−)- and (+)-kainic acid using a planar chiral amide as a chiral building block

Both enantiomers of kainic acid have been synthesized from enantioenriched planar chiral cyclic amide 2a. The C3 and C4 stereocenters in the pyrrolidine ring were constructed by transannular Cope rearrangement of 2a, and the carboxyl group at the C2 position was introduced through lithiation followed by a carboxylation in the presence of an external chiral ligand.     

Asymmetric synthesis of 1-deoxynojirimycin and its congeners from a common chiral building block

A new, promising chiral building block 9 for the synthesis of 1-deoxy-4,5-trans-oriented azasugars such as 1-deoxynojirimycin (1) was prepared in only four steps from the Garner aldehyde 10 using catalytic ring-closing metathesis (RCM) for the construction of the piperidine ring. In practical test, the first synthesis of all four isomers (1 and 6-8) of trans-4,5-orientated 1-deoxyiminosugars using 9 as a common chiral building block was demonstrated.     

delta-Amino beta-keto esters, a designed polyfunctionalized chiral building block for alkaloid synthesis. Asymmetric synthesis of (R)-(+)-2-phenylpiperidine and (-)-SS20846A

[formula: see text] delta-Amino beta-keto esters 3 and 11 are designed polyfunctionalized chiral building blocks for alkaloid synthesis and are prepared in one step from the corresponding sulfinimine (N-sulfinyl imine). Concise highly enantioselective four-step syntheses of 2-phenylpiperidine (7) and SS20846A (14) from 3 and 11, respectively, are described.     

A concise synthesis of (+)-pancratistatin using pinitol as a chiral building block

A concise approach toward (+)-Pancratistatin has been achieved via 12 steps from pinitol. An ultrasound assisted arylcerium induced ring opening of cyclic sulfate was employed as a key step.     

Asymmetric synthesis of the carbocyclic nucleoside building block (R)-(+)-4-aminocyclopentenone using delta-amino beta-ketophosphonates and ring-closing metathesis (RCM)

Amino keto-2,7-dienes undergo ring-closing metathesis (RCM) to give 4-aminocyclopentenones, valuable intermediates in the asymmetric construction of carbocyclic nucleosides. The key amino ketodienes were prepared using delta-amino beta-ketophophonates, a new sulfinimine-derived chiral building block, and HWE chemistry. [reaction: see text]     

Asymmetric synthesis of a chiral building block for cyclopentanoids: a novel enantioselective synthesis of preclavulone A

A new asymmetric approach to the hydroxylactone (+)-(3aR,4R,6aS)-4-(hydroxymethyl)-3a,4-dihydro-3H-cyclopenta[b]furan-2(6aH)-one (1), a key synthetic building block for cis-1,2-disubstituted five-membered ring derivatives (i.e., isoprostanes, jasmonates, and clavulones), has been described. A remarkable control of the absolute and relative configuration of the three stereocenters was achieved. Thus, the use of the Trost's asymmetric allylic alkylation strategy secured highly enantioenriched (R)-3-(nitromethyl)cyclopent-1-ene (13), which was smoothly converted to (R)-cyclopent-2-enecarboxylic acid (15) in excellent yield and high enantiomeric purity (>98% ee). 6-exo-trig atom-transfer radical cyclizations of ((R)-cyclopent-2-enyl)methyl 2-iodoacetate (12) produced exclusively the desired cis-fused delta-lactone (4aR,7aR)-hexahydro-5-iodocyclopenta[c]pyran-3(1H)-one (11), which was subsequently elaborated to hydroxylactone 1 through a stereocontrolled Pd(II)-mediated lactonization reaction. En route to preclavulone A, a putative elusive intermediate in the biosynthesis of clavulones, the synthetic utility of compound 1 was demonstrated. The key feature in this synthesis was the installation of the lower side chain via the Knochel organozinc sp3-sp C-C coupling protocol.     

用(R)-(+)-缩水甘油的亲核开环反应制备手性连二醇

以D-甘露醇为原料合成(R)-(+)-缩水甘油1。该环氧化合物的亲核开环反应为高立体选择性地(93%-96%e.e.)制备各种手性连二醇提供了一条简便途径。     

Asymmetric synthesis of (+)-galbelgin, (-)-kadangustin J, (-)-cyclogalgravin and (-)-pycnanthulignenes A and B, three structurally distinct lignan classes, using a common chiral precursor

The enantioselective synthesis of three structurally distinct classes of lignan from a single, aza-Claisen-derived, chiral morpholine amide is reported. The class of lignan formed is dependent on the substitution pattern in the aryl rings and choice of protecting group on a key benzylic hydroxyl group. The methodology has been used to asymmetrically synthesize and determine the absolute stereochemistry of lignans (+)-cyclogalgravin 3, (-)-pycnanthulignene A 4, (-)-pycnanthulignene B 5, and (-)-kadangustin J 8.     

A new convergent route to aldohexoses from a common chiral building block

[reaction in text] A diastereocontrolled route to the eight aldohexoses has been developed starting from a common cyclohexanoid chiral building block.     

One-pot synthesis of chiral nonracemic amines

One-pot five-component reactions of oxathiazolidine-S-oxides with mesitylmagnesium bromide, lithium bis(trimethylsilyl)amide, aldehydes and Grignard reagents afford chiral nonracemic amines or sulfinamides in good yields and high stereoselectivities.     

Asymmetric synthesis of (-)-7-epiaustraline and (+)-1,7-diepiaustraline

A diastereoselective and modular approach to the synthesis of the 3-hydroxymethyl-2,3,5,6,7,7a-hexahydro-1H-pyrrolizine-1,2,7-triol structure, characteristic of several natural pyrrolizidine natural products, has been developed. This approach culminated in the synthesis of (-)-7-epiaustraline and (+)-1,7-diepiaustraline. The oxazolidinone group has been found to be a useful protecting group in the RCM reaction and, as part of a pyrrolo[1,2-c]oxazol-3-one ring system, has functioned as a stereo- and regio-directing group in a key diastereoselective cis-dihydroxylation reaction and a regioselective nucleophilic ring-opening of a S,S-dioxo-dioxathiole.     

Asymmetric synthesis of (+)-cis-nemorensic acid from a chiral Diels-Alder adduct of 2,5-dimethylfuran

(+)-cis-Nemorensic acid was synthesized from a chiral Diels-Alder adduct prepared by a catalytic enantioselective Diels-Alder reaction with 2,5-dimethylfuran and 2,2,2-trifluoroethyl acrylate.     

Asymmetric synthesis of (+)-lentiginosine using a chiral aziridine based approach

The synthesis of the indolizidine alkaloid, (+)-lentiginosine, is described. A key feature of the preparative route is the efficient and stereoselective construction of a dihydroxylated pyrrolidine via Sharpless asymmetric dihydroxylation of an aziridine-enoate, which was prepared from commercially available 1-(S)-α-methylbenzylaziridine-2-methanol. In addition, a regioselective aziridine-to-pyrrolidinone ring expansion process followed by a Wittig olefination was employed to construct a late stage pyrrolidine intermediate that was transformed into (+)-lentiginosine.     

Asymmetric synthesis of (-)-swainsonine, (+)-1,2-di-epi-swainsonine,and (+)-1,2,8-tri-epi-swainsonine

The asymmetric synthesis of (-)-swainsonine via a nonchiral pool route that involves the Sharpless epoxidation to induce chirality is reported. The key steps involve vinyl epoxide aminolysis, ring-closing metathesis, and intramolecular N-alkylation to prepare the indolizidine ring and a highly diastereoselective cis-dihydroxylation using AD-mix-alpha. This synthetic strategy also allowed for the diastereoselective synthesis of (+)-1,2-di-epi-swainsonine and (+)-1,2,8-tri-epi-swainsonine.     

A new convergent route to conduritols A-F from a common chiral building block

A diastereocontrolled route to conduritols A-F has been developed starting from a common chiral building block containing an oxabicyclo[3.2.1]octane framework.     

Asymmetric 1,3-dipolar cycloadditions of a chiral nonracemic glyoxylic azomethine imine

The reactivity of a chiral nonracemic glyoxylic azomethine imine has been investigated. This species reacts with a wide range of dipolarophiles, with a complete regio- and facial stereoselectivity. The introduction of an electron-withdrawing substituent on the ylide leads to a lower endo selectivity with electron-withdrawing dipolarophiles, but to an improved exo selectivity with styrene derivatives when compared to the reactivity of aliphatic- or aromatic-substituted ylides.     

Total synthesis of (+)-epiepoformin, (+)-epiepoxydon and (+)-bromoxone employing a useful chiral building block, ethyl (1R,2S)-5,5-ethylenedioxy-2-hydroxycyclohexanecarboxylate

Enantioselective total synthesis of (+)-epiepoformin 1, (+)-epiepoxydon 2 and (+)-bromoxone 3 using a chiral building block, ethyl (1R,2S)-5,5-ethylenedioxy-2-hydroxycyclo- hexanecarboxylate 6, is described. Since the synthesis afforded intermediates 18, 2 and 25, it accomplished a formal synthesis of (−)-theobroxide 19, (−)-phyllostine 22, (+)-herveynone 27 and (−)-asperpentyn 28. The usefulness of 6 for the synthesis of natural epoxycyclohexene derivatives was demonstrated.     

Asymmetric synthesis of sulfinamides using (-)-quinine as chiral auxiliary

A process has been designed and demonstrated for the asymmetric synthesis of sulfinamides using quinine as auxiliary. A variety of chiral sulfinamides including N-alkyl sulfinamides with diverse structure were prepared in good yields and excellent enantioselectivity starting from easily available and inexpensive reagents. The auxiliary quinine could be recovered and recycled.     

Asymmetric synthesis of (R)-(+)-etomoxir via enzymatic resolution

An asymmetric synthesis of (R)-(+)-etomoxir 3, employing enzymatic resolution of ethyl 2-alkyl-2,3-dihydroxypropionate using Amano AK via transacylation is reported.