Formal total synthesis of (-)-emetine using catalytic asymmetric allylation of cyclic imines as a key step

[reaction: see text] Catalytic asymmetric allylation of 3,4-dihydro-6,7-dimethoxyisoquinoline was carried out using allyltrimethoxysilane in the presence of Cu(I) and tol-BINAP. The allyl adduct thus obtained was transformed to a chiral synthetic intermediate for (-)-emetine in good yield. The procedure was applied to the total synthesis of ent-emetine.     

Facile synthesis of (±)-, (+)-, and (-)-galanthamine

The Amarylidacea alkaloid galanthamine ( 1a ) is an acetylcholinesterase inhibitor that has been evaluated as a potential agent for the treatment of Alzheimer's disease. We report a very efficent synthesis of (±)-galanthamine [(±)- 1a ] from readily available isovanillin and tyramine. We have separated racemic galanthamine into its diastereoisomeric (1S)-camphanate esters and obtained both natural (-)- and unnatural (+)-galanthamine by lithium aluminum hydride removal of the acyl group.     

The synthesis of 2-benzazocines using ring-closing metathesis as a key step

A number of protected 7-isopropoxy-8-methoxy-1,2,3,6-tetrahydro-2-benzazocines were synthesized from 2-allyl-3-isopropoxy-4-methoxybenzaldehyde using ring-closing metathesis as the key step. In addition, two 9-isopropoxy-8-methoxy-3,6-dihydro-2-benzazocines were synthesized from 5-isopropoxy-4-methoxy-2-[(1E)-3-phenyl-2-propenyl]benzaldehyde, which in turn was obtained from the thermal Claisen-Cope rearrangement of 4-methoxy-3-{[(2E)-3-phenyl-2-propenyl]oxy}benzaldehyde. Finally, five of the 2-benzazocine compounds were tested for anti-cancer activity.     

Total synthesis of (±)-dihydroactinidiolide using selenium-stabilized carbenium ion

A new, short total synthesis of dihydroactinidiolide 1 is described using selenium carbenium ion-promoted carbon–carbon bond formation as the key step. Our synthetic strategy starts with a lactonization reaction between 1,3,3-trimethylcyclohexene 13 and α-chloro-α-phenylseleno ethyl acetate 14, affording the key intermediate, α-phenylseleno-γ-butyro lactone 15, which reacted via a selenoxide elimination to the target compound 1.     

Total synthesis of (±)-fangchinoline

(±)-Fangchinoline was synthesized by condensation of (±)-1-(3-bromo-4-methoxy-benzyl)-2-methyl-6-methoxy-7-hydroxy-8-bromo-1,2,3,4-tetrahydroisoquinoline ( 2 ) and (±)-1-(4-hydroxy-benzyl)-2-methyl-6-methoxy-7-hydroxy-1,2,3,4-tetrahydroisoquinoline ( 3 ) in the presence of copper, pyridine and potassium carbonate.     

Total synthesis of (−)-elegansidiol by using an abnormal Beckmann fragmentation of Hajos ketone oxime as a key step

Abnormal Beckmann fragmentation of Hajos ketone oxime regioselectively forms of a chiral 1-oxygenated 2,2-dimethyl-4-methylene-cyclohexan skeleton. Using this transformation as a key step, the total synthesis of (−)-elegansidiol, an oxygenated mono-carbocyclic sesquiterpenoid, was achieved.     

General method for the synthesis of substituted phenanthridin-6(5H)-ones using a KOH-mediated anionic ring closure as the key step

Substituted phenanthridin-6(5H)-ones were obtained in a two-step procedure involving a Suzuki cross-coupling reaction followed by a KOH-mediated anionic ring closure. The influence of the nature and the position of the substituents on the cyclization step were studied. This methodology offers a general and practical route to diversely substituted phenanthridin-6(5H)-ones.     

Spirocyclization strategy toward indole phytoalexins. The first synthesis of (±)-1-methoxyspirobrassinin, (±)-1-methoxyspirobrassinol, and (±)-1-methoxyspirobrassinol methyl ether

The first syntheses of cruciferous indole phytoalexins (±)-1-methoxyspirobrassinin, (±)-1-methoxyspirobrassinol, (±)-1-methoxyspirobrassinol methyl ether as well as a new syntheses of phytoalexins (±)-spirobrassinin and cyclobrassinin were achieved by dioxane dibromide (DDB)-mediated spirocyclization of brassinin and its 1-substituted derivatives.     

The total synthesis of (±)-coriolin

The first total synthesis of (±)-coriolin from the tricyclo 6-4-5-fused ring photo-adduct through the key tricyclo 5-5-5-fused ring intermediate, 7,8,11 - trihydroxy - 1,4,4 - trimethyltricyclo[6.3.0.0^2,6]undecan - 3 - one, is described.     

A stereospecific synthesis of (±)-ferruginol

A stereospecific synthesis of (±)-ferruginol following the Robinson “ring extension” method has been described. The infra-red spectra of the benzoates of the synthetic and natural ferruginol are found to be identical.     

Efficient asymmetric synthesis of (S)- and (R)-N-Fmoc-S-trityl-alpha-methylcysteine using camphorsultam as a chiral auxiliary

(1R)-(+)-2,10- and (1S)-(-)-2,10-camphorsultam were acylated with ethyl 2-phenylthiazoline 4-carboxylate to afford (+)- and (-)-2-phenylthiazolinylcamphorsultam, which were stereoselectively alkylated with MeI in the presence of n-BuLi. Alkylation of these phenylthiazolinylcamphorsultams occurred from the beta-face rather than alpha-face, resulting in the formation of (S)-alpha-methylcysteine from (1R)-(+)-2,10-camphorsultam and (R)-alpha-methylcysteine from (1S)-(-)-2,10-camphorsultam after acidic hydrolysis. Subsequent protection of the side chain thiol group with trityl alcohol and alpha-amine function with Fmoc-OSu furnished fully protected (S)- and (R)-N-Fmoc-S-trityl-alpha-methylcysteine in overall 20% yield.     

Formal synthesis of salinosporamide A using a nickel-catalyzed reductive aldol cyclization-lactonization as a key step

Application of a sequential nickel-catalyzed reductive aldol cyclization-lactonization reaction in a short formal synthesis of salinsporamide A, a potent 20S proteasome inhibitor and anti-cancer compound, is described.     

First total synthesis of (±)-oxerine

Total synthesis of (±)-oxerine (1), a monoterpene alkaloid, starting from 3-bromopyridine (7) is described. The key reaction in this sequence is the samarium iodide (SmI₂)-mediated intramolecular cyclization of γ-ethynyl bromide (4).     

Enzymatic resolution of a quaternary stereogenic centre as the key step in the synthesis of (S)-(+)-citalopram

The enzymatic resolution of 4-[(4-dimethylamino)-1-(4^′-fluorophenyl)-1-hydroxy-1-butyl]-3-(hydroxymethyl)-benzonitrile, a useful intermediate in the synthesis of enantiomerically pure citalopram, has been studied. Candida antarctica lipase B (CAL-B) catalyzes the enzymatic acetylation of the primary benzylic alcohol with high enantioselectivity at the quaternary stereogenic centre. The enzymatic enantioselective hydrolysis of the 3-acetyloxymethyl derivative catalyzed by CAL-B is also possible.     

The chemistry of vicinal tricarbonyls : A synthesis of (±)-slaframine and (±)-6-epi-slaframine

A synthesis of (±)-slaframine and (±)-6-epi-slaframine is described. The approach makes use of the intramolecular alkylation of an N-substituted 3-hydroxypyrrole-2-carboxylate ester.     

Microwave-assisted solid-phase organic synthesis (MASPOS) as a key step for an indole library construction

[reaction: see text] Microwave-assisted solid-phase organic synthesis (MASPOS) has been demonstrated to significantly facilitate the Cu(II)- or Pd(II)-mediated ring closure of the resin-bound 2-alkynylanilides. Under microwave irradiation at 200 degrees C [for Cu(OAc)(2), NMP] or 160 degrees C [for Pd(MeCN)(2)Cl(2), THF] for 10 min, 1-acyl-2-alkyl-5-arenesulfamoylindoles were obtained, after cleavage from the resin, in 95-99% purities and in 65-82% overall yields via a 5-step synthetic sequence.     

A stereocontrolled total synthesis of (±)-norzizanone

A stereocontrolled total synthesis of (±)-norzizanone 1 has been efficiently accomplished involving base-induced rearrangement of the mesylate 17 as the key step. Aryl participated intramolecular cyclisation of the bromophenol 11 provided the tricyclic dienone 12, which was stereoselectively converted into the mesylate 17.     

A facile synthesis of the basic steroidal skeleton using a Pauson-Khand reaction as a key step

A high-yield synthesis of steroid-type molecules under mild reaction conditions is achieved in two steps involving nucleophilic addition of alkynyl cerium reagent to an easily enolizable carbonyl compound (beta-tetralone) followed by an intramolecular Pauson-Khand reaction.