A short synthesis of (+)-hygrine

The synthesis of the alkaloid hygrine in a series of six steps starting from readily available proline N-methyl derivative (5) is described.     

A short total synthesis of (+)-furanomycin

[reaction: see text] Furanomycin is a Streptomyces metabolite that substitutes for isoleucine in protein translation. We report a concise and modular synthesis starting from the Garner aldehyde and proceeding in seven steps to furanomycin. The key steps include a stereoselective acetylide addition and the Ag+-mediated cyclization of an alpha-allenic alcohol to construct the trans-2,5-dihydrofuran. The efficiency (12% overall yield) and flexibility of the route will provide ample quantities of furanomycin and analogues for protein engineering.     

A short stereoselective synthesis of (+)-boronolide

A short and stereoselective synthesis of (+)-boronolide via oxidative functionalization of an olefin using a pendant sulfinyl group is described. Diastereoselective allylation was performed using Keck’s protocol and the lactone moiety was prepared by ring closing metathesis.     

A short enantioselective synthesis of (+)-eleutherin, (+)-allo-eleutherin and a formal synthesis of (+)-nocardione B

A short enantioselective synthesis of (+)-eleutherin, (+)-allo-eleutherin and the formal synthesis of (+)-nocardione B is described. The synthesis is completed in six steps in overall yields of 8% for eleutherin and 14% for allo-eleutherin. The synthetic strategy features an efficient combination of the Dötz annulation reaction with a chiral alkyne and an oxa-Pictet Spengler reaction as the keys steps in the stereodivergent synthesis of (+)-eleutherin and (+)-allo-eleutherin. The synthesis of (S)-(+)-2-(2′-hydroxypropyl)-5-methoxy-1,4-naphthoquinone entails the formal synthesis of (+)-nocardione B.     

A short asymmetric synthesis of (+)-lyoniresinol dimethyl ether

A short, efficient synthesis of the lignan (+)-lyoniresinol dimethyl ether is described. The synthesis is achieved by asymmetric photocyclization of an achiral dibenzylidenesuccinate to a chiral aryldihydronaphthalene. (-)-Ephedrine is used as a chiral auxiliary to bias the atropisomeric equilibrium in the dibenzylidenesuccinate prior to the photochemical reaction. The synthesis of the title compound was accomplished in five steps, and the final product was recrystallized to constant melting point and rotation.     

A short stereoselective synthesis of (+)-aza-galacto-fagomine (AGF)

A catalytic asymmetric synthesis of (+)-aza-galacto-fagomine (AGF) – the most promising compound for the pharmacological chaperone therapy of Krabbe disease – was accomplished in six steps, in 14% overall yield. The synthesis hinges on the combination of organocatalyzed aldolization and reductive hydrazination.     

A short and efficient synthesis of (+)-disparlure and its enantiomer

A short and highly efficient approach was applied for the total synthesis of the gypsy moth sex pheromone (+)-disparlure and its enantiomer from isopropylidene D- and L-erythrose, using a common strategy.     

A short synthesis of (+) and (−)-falcarinol

A short, practical synthesis of the bis-acetylenic natural product falcarinol 1 is reported. This method relies on the alternate functionalisation of bis-trimethylsilylbutadiyne 10. This may be achieved in one-pot, however, better yields were obtained more conventionally. Lipase mediated enzymatic kinetic resolution of the racemic adduct in an organic solvent afforded (+)-1 in 97% enantiomeric excess. The analogous process performed with racemic 3-acetoxy falcarinol 11 under aqueous conditions gave (−)-1. Oxidation of 1 with Dess-Martin periodinane gave falcarinone 2.     

A short and efficient stereoselective synthesis of the polyhydroxylated macrolactone (+)-aspicillin

[structures: see text] A short and efficient synthesis of the polyhydroxylated macrolactone (+)-aspicilin 1 using a stereoselective lithium perchlorate mediated addition of allyltributyltin to the equatorially disposed carboxaldehyde of 3 (derived from (R',R',R,S) butane diacetal protected butane tetrol 2) as the key step is described. Terminal group manipulation and Masamune-Roush olefination using phosphonate ester 4 followed by macrocyclization via ring closing metathesis afforded the natural product after partial hydrogenation and global deprotection.     

Enantiodivergent formal synthesis of (+)- and (-)-cyclophellitol from D-xylose based on the latent symmetry concept

Formal synthesis of (+)- and (-)-cyclophellitol from d-xylose has been accomplished through utilization of the latent plane of chirality present in the starting carbohydrate. The synthetic pathway is suitable for preparation and biological evaluation of cyclophellitol analogues in both enantiomeric series.     

Total synthesis of Angucyclines. Part 18: A short and efficient synthesis of (+)-ochromycinone

A short and highly enantiospecific (seven steps, 99% ee) synthesis of (+)-ochromycinone 2 in 19% overall yield is reported. Key steps are the regioselective Diels–Alder reaction of the juglone derivative 4 with the mixture of dienes 5 and 9 derived from 3-methylcyclohexanone (99% ee) and the photooxidation of 1-deoxyochromycinone 3 to the natural ketone 2. A pronounced concentration dependence of the specific rotation was observed for (+)-ochromycinone 2 in CHCl₃.     

A short synthesis of the anti-leukemic sesquiterpene (+)-caparratriene employing aqueous Wittig chemistry

An efficient, stereoselective method for the synthesis of (+)-caparratriene based on an aqueous Wittig reaction has been developed. A functionalized triethylallyl ylide reacted under various conditions with (+)-citronellal to deliver (+)-caparratriene in only three steps with excellent overall yield. The Wittig reaction proceeded with exclusive (4E)-selectivity and an interesting cationic effect was uncovered with good stereoselectivity at the isomerizable allylic position being observed in the presence of lithium salts.     

Conversion of D-glucose to cyclitol with hydroxymethyl substituent via intramolecular silyl nitronate cycloaddition reaction: application to total synthesis of (+)-cyclophellitol

[reaction: see text] A diastereoisomeric mixture of 1-nitro-6-heptene-2,3,4,5-tetraol derivative (A) was prepared by Henry reaction between d-glucose-based aldehyde and nitromethane. Only the (2S)-isomer of A led to cyclitol (B) via nitronate-olefin cycloaddition on treatment with TMS-Cl and Et(3)N in the presence of catalytic DMAP followed by acid treatment. (+)-Cyclophellitol (1) was synthesized from B in eight steps.     

A short enantioselective synthesis of (+)-L-733,060 via Shi epoxidation of a homoallylic carboxylate

A short and efficient enantioselective synthesis of (+)-L-733,060 in 92% ee via Shi epoxidation of a homoallylic carboxylate is described. Johnson-Claisen rearrangement was employed to obtain the required carbon backbone, whilst intramolecular reductive O-to-N-ring expansion of a δ-azidolactone was used in the construction of the piperidine moiety.     

A synthesis of (+)-saxitoxin

An asymmetric synthesis of the bis-guanidinium poison, (+)-saxitoxin (STX), is described. Commencing from an N,O-acetal starting material made readily available through sulfamate ester C-H amination, the completed route to STX showcases the utility of oxathiazinane dioxide heterocycles for the assembly of polyfunctionalized amine derivatives. In the final preparative stages, an unusual nine-membered ring guanidine intermediate is oxidized selectively and made to undergo dehydrative cyclization to afford the tricyclic core of the natural product. Access to STX and related structures will provide unique pharmacological tools for the study of voltage-regulated Na+ ion channel proteins.     

A synthesis of (+)-salvadione-A

[reaction: see text] The p-benzoquinone shown is converted to the novel hexacyclic triterpene salvadione-A in four steps.     

A short enantioselective synthesis of (−)-chloramphenicol and (+)-thiamphenicol using tethered aminohydroxylation

An efficient enantioselective synthesis of (−)-chloramphenicol (1) and (+)-thiamphenicol (2) is described. These antibiotics have been synthesized from commercially available 4-nitrobenzaldehyde and 4-(methylthio)benzaldehyde, respectively, using tethered aminohydroxylation and Sharpless asymmetric epoxidation as the chirality inducing steps.     

Total synthesis of (+)-belactosin A

A concise first total synthesis of the antitumour antibiotic belactosin A is reported, involving coupling of beta-lactone carboxylic acid 3 with N-Ala-aminocyclopropyl alanine 11.     

Total synthesis of (+)-macquarimicin A

The first total synthesis of (+)-macquarimicin A (1), a novel inhibitor of neutral sphingomyelinase (N-SMase) with antiinflammatory activity, has been accomplished. The present work determined the absolute configuration of (+)-1 and revised the C(2)-C(3) geometry to be Z. The synthesis features a transannular Diels-Alder reaction, which constructed the tetracyclic framework stereoselectively, and a convergent and efficient synthetic pathway, which afforded (+)-macquarimicin A (1) in 27 steps (longest linear sequence) with 9.9% overall yield.     

A practical synthesis of (+)-cocaine

(+)-Cocaine has been prepared from commercially available 3-tropinone in four steps. Synthetic procedures and experimental details are provided.