Synthetic studies on carbapenem antibiotics from penicillins. IV. Stereoselective kinetic protonation of a chiral azetidinone enolate

A stereoselective kinetic protonation of the azetidinone enolate $\text{B}$ was studied and an efficient synthesis of$\text{2}$(cis) was achieved via aldol reaction of $\text{5}$ with acetone followed by the kinetic protonation with Ph₃SnH as proton source.     

Synthetic studies on carbapenem antibiotics from penicillins.II. regio- and stereoselective aldol reaction of a chiral azetidinone: a synthesis of optically active 6-epicarpetimycins

Aldol and alkylation reactions of the chiral 4-allylazetidinone 1 gave 3,4-trans-azetidinones as major products, in which 10 was converted in several steps to the optically active 6-epicarpetimycins 2.     

Stereoselective and efficient total synthesis of optically active tetrodotoxin from D-glucose

A stereoselective and efficient total synthesis of optically active tetrodotoxin (TTX) is described. A polyfunctionalized key cyclitol compound containing branched-chains for the synthesis of TTX was prepared from D-glucose employing the Henry reaction (Nitro aldol reaction) as the key transformation. Stereoselective construction of the alpha-azido-aldehyde branched-chain was achieved via the key spiro alpha-chloroepoxide intermediate.     

Synthetic studies of carbapenem and penem antibiotics. III. A synthesis of a key intermediate for 1 beta-methylcarbapenem.

We synthesized useful intermediates 5 and 6 for 1 beta- and 1 alpha-methylcarbapenems from 4-carboxy-3-[(R)-1-hydroxyethyl]-2-azetidinone 4 as a starting material by using stereoselective hydrogenation and hydroboration, respectively. A practical synthetic route from 4 to the (3S,4S)-4-[(R)-1-carboxyethyl]-3-[(R)-1-hydroxyethyl]-2-azetidinone derivative 1, a useful intermediate for the synthesis of 1 beta-methylcarbapenem antibiotics, was established.     

Synthetic studies on (+)-aplasmomycin. 2. Stereoselective synthesis of Corey''s key intermediate, a formal total synthesis

The C-3 C-11 segment of (+)-aplasmomycin was synthesized stereoselectively starting from (+)-pantolactone ( ) and the C-3 C-17 segment was synthesized via coupling of and .     

Synthetic studies on β-lactam antibiotics. Part 16. synthesis of 1-carba-2-penem-3-carboxylic acid esters from penicillins utilizing a carbon-carbon coupling reaction

Allylazetidinones $\text{9}$, $\text{10}$, prepared by coupling of allylcoppers $\text{8}$ with chloroazetidinones $\text{6}$, $\text{7}$, were converted into carbapenem esters $\text{16}$, $\text{28}$–$\text{31}$ using an Emmons-Horner reaction to introduce the 6-side chain and an intramolecular Wittig reaction to form the carbapenem ring system.     

Synthetic studies on maitotoxin. 3. Stereoselective synthesis of the BCDE-ring system

The stereoselective synthesis of the BCDE-ring system of maitotoxin has been accomplished through a two-directional strategy for the construction of polycyclic ether. The key reactions involve SmI 2-induced double cyclization of a beta-alkoxyacrylate and a double dihydroxylation for construction of the B- and E-rings.     

Synthetic studies on β-lactam antibiotics. part 11. Completely stereocontrolled synthesis of 7α-unsubstituted 1-oxacephems from penicillins

A $\text{cis}$ intermediate $\text{3}$ was obtained by novel reductive cleavage of $\text{2}$, prepared from $\text{1}$ in $\text{6}$ steps including a new ester to ketone conversion. Regioselective bromination of $\text{3}$ followed by substitution and known conversions gave 1-oxacephems $\text{5}$.     

Synthetic studies on arene-olepin cycloadditions-VII:1 a three-step total synthesis of (±)-silphinene

A three-step total synthesis of (±)-silphinene ($\text{1}$) is described which illustrates the high process selectivity attainable with the arene-olefin metaphotocycloaddition and a method for selective transformation of metacycloadducts.     

Asymmetric synthesis by chiral cobalt catalysts: Homogeneous reduction of ketones to optically active alcohols

The hydrogenation of ketones with Co₂(CO)₆(PR₃)₂ (PR₃ = PPh₂-neomenthyl, PPh₂ -6-deoxo-1,2:3,4-diisopropylidene d-galactose and PMe₂ -menthyl) as catalysts gives optically active alcohols in optical yields of 1.6 to 5%.     

Synthetic studies on maitotoxin. 2. Stereoselective synthesis of the WXYZA'-ring system

The stereoselective synthesis of the WXYZA'-ring system of maitotoxin has been accomplished via a linear synthetic approach, in which key reactions were SmI 2-induced cyclization of beta-alkoxyacrylate for the construction of the A'-, Y-, and X-rings and 6- endo cyclization of hydroxy vinylepoxide for that of the Z- and W-rings.     

Stereoselective aldol reactions of dihydroxyacetone derivatives catalyzed by chiral Zn2+ complexes

The direct aldol reaction between a protected dihydroxyacetone derivative and 4-nitrobenzaldehyde catalyzed by chiral Zn²⁺ complexes of 1-(n-carboxylalkyl)-7-aminoacyl-1,4,7,10-tetraazacyclododecane is reported. New Zn²⁺ complexes containing l-histidine and carboxylalkyl chains that mimic a class II aldolase, carboxypeptidase A and a serine protease were designed and synthesized. Syn-aldol products were mainly formed by an aldol reaction of acetonide-protected dihydroxyacetone with benzaldehydes and other benzaldehydes in N-methylpyrrolidone (NMP)/alcohol (MeOH, EtOH or 2-PrOH) in good yields with a high degree of diastereo- and enantioselectivity (56%～quant., 57～>99% ee). Mechanistic aspect based on ESI-HRMS, elemental analysis and pH titrations of model ligands is also discussed.     

Shikimate-derived metabolites. 14.1 chiral synthesis of 5-enolpyruvyl-shikimate-3-phosphate

The title compound, a key biosynthetic intermediate in the shikimate metabolic pathway, has been synthesized in good yield from (?)-shikimic acid ($\text{1}$).     

Stereoselective synthesis of 3-substituted tetrahydroisoquinolines from phthalan and chiral N-sulfinylimines

The reaction of the dianionic intermediate [resulting from the reductive opening of phthalan (1) with lithium] with chiral N-tert-butylsulfinyl aldimines 3 in the presence of ZnMe₂ gives, after hydrolysis, N-tert-butylsulfinyl amino alcohols 4 with high diastereoselectivity. Successive treatment of compounds 4 with hydrogen chloride in methanol, thionyl chloride in chloroform and sodium hydroxide yields 3-substituted tetrahydroisoquinolines 6.     

Synthesis of optically active derivatives of bicyclic chiral diols with C2 symmetry

This paper reports efficient procedures for the preparation of optically active dibromide, diazide, diamine, and unsaturated diesters derived from a chiral bicyclic diol with C₂ symmetry namely (11R,12R)-9,10-dihydro-9,10-ethaneanthracene-11,12-dimethanol 3. Esterification of 3 with saturated and unsaturated carboxylic acids and acids chlorides leads to the corresponding normal-, olefinic- and acetylenic diesters in average yields of 81%. Also more efficient techniques for the preparation of starting diol 3 in higher yields as well as for a very simple separation of DCU (N,N′-dicyclohexylurea) from reactions carried out following the DCC/DMAP method are described.     

Synthetic studies on amipurimycin: total synthesis of a thymine nucleoside analogue

Amipurimycin, a member of the complex peptidyl nucleoside family of antibiotics, is a Streptomyces-derived potent antifungal agent. The mechanism of action of amipurimycin, however, remains undetermined. Additionally, there are no reports on the total synthesis or structure-activity relationships (SAR) of this potentially useful bioactive compound. In a study aimed at the total synthesis and SAR studies of this natural product, the present research reports the development of a synthetic route to the central pyranosyl amino acid core of amipurimycin and its further elaboration, culminating in the synthesis of a unique thymine analogue. Utilizing a d-serine-derived dihydroaminopyrone as a strategic building block, the synthesis involves de novo construction of the fully functionalized C-3-branched carbohydrate amino acid core, followed by glycosidic attachment of thymine at C-1, and peptidic linking of the C-6 amine with the 1,2-aminocyclopentane carboxylic acid side chain.     

Synthetic studies on cyathins: enantioselective total synthesis of (+)-allocyathin B2

[reaction: see text] The enantioselective total synthesis of (+)-allocyathin B(2) has been achieved. Our approach features a convergent enantioselective construction of the 5-6-7 tricyclic core system using the originally developed chiral building blocks via asymmetric catalysis, the intramolecular aldol reaction in high yield, successful samarium diiodide-mediated ring expansion, and a newly developed double-bond installation method.