Total synthesis of (±)-stemonamide, (±)-isostemonamide, (±)-stemonamine, and (±)-isostemonamine using a radical cascade

A total synthesis of (±)-stemonamide and (±)-isostemonamide has been achieved by using a radical cascade that involves two endo-selective cyclizations. (±)-Stemonamine and (±)-isostemonamine are synthesized by chemoselective reduction of (±)-stemonamide and (±)-isostemonamide, respectively.     

A general approach to crinine-type Amaryllidaceae alkaloids: total syntheses of (±)-haemanthidine, (±)-pretazettine, (±)-tazettine, and (±)-crinamine

A general strategy for synthesizing the crinine-type Amaryllidaceae alkaloids was developed. And total syntheses of four representative crinine-type Amaryllidaceae alkaloids: (±)-haemanthidine, (±)-pretazettine, (±)-tazettine, and (±)-crinamine, were accomplished via a common intermediate 17. This crucial precursor was achieved on the basis of the NBS-promoted semipinacol rearrangement recently developed by our group and an intramolecular Michael addition, which efficiently constructed the sterically congested quaternary carbon center and the hydroindole skeleton of the crinine-type alkaloids, respectively.     

Concise total syntheses of (±)isopaucifloral F, (±)quadrangularin A, and (±)pallidol

Concise total syntheses of (±)isopaucifloral F, (±)quadrangularin A, and (±)pallidol, starting from commercially available 3,5-dimethoxybenzoic acid, have been achieved by a sequential process. The overall synthetic strategy involves Nazarov cyclization, Ramberg-Backlund olefination, and Friedel-Crafts alkylation.     

Total synthesis of (±)-brazilin and formal synthesis of (±)-brazilein, (±)-brazilide A using m-CPBA

Total synthesis of (±)-brazilin has been accomplished. m-CPBA epoxidation of allyl alcohol 10 and epoxy opening reaction mediated by m-chlorobenzoic acid, formed in situ as a byproduct, gave advanced intermediate diol 14. O-alkylation and cyclization gave phenol 6 which enabled the formal synthesis of (±)-brazilein and (±)-brazilide A.     

Protecting group free syntheses of (±)-columbianetin and (±)-angelmarin

A five-step and protecting group free synthesis of (±)-columbianetin from cyclohexane-1,3-dione is reported. The former compound was converted into its p-hydroxycinnamate derivative, (±)-angelmarin, using Coster’s esterification procedure. Efforts to modify the synthesis so as to prepare angelmarin and columbianetin in an enantioselective manner are described.     

Stereocontrolled total syntheses of (±)-clovan-3-one and (±)-epi-clovan-3-one and a facile total synthesis of (±)-pseudoclovene-A

Stereocontrolled total syntheses of the bridged tricyclic ketones (±)-clovan-3-one (5) and (±)-epi-clovan-3-one (6) and a facile total synthesis of the tricyclic sesquiterpene (±)-pseudoclovene-A (3) have been successfully accomplished involving participation of an aryl intramolecular cyclisation of the bromophenol 11 as a key step.     

Synthetic studies towards furosesquiterpenoids: total synthesis of (±) desmethylpallescensin-A, (±) isopallescensin-A and (±) isopallescensin-1

A new approach for a short and efficient synthesis of common cyclohexenone intermediate towards the total synthesis of some furosesquiterpenes and their analogues are described. Regioselective alkylation of Hagemann's ester with 2/3-furyl-2-ethyl bromide followed by hydrolysis cum in situ decarboxylation and 1,4-addition with Gilman's reagent produced the cyclohexanone derivatives which have been utilized for total synthesis of (±) isopallescensin-A, (±) 10-desmethylpallescensin-A, (±) 5-desmethyl-4,5-dehydromicrocionin-1 and (±) isopallescensin-1.     

Stereoselective total synthesis of (±)-α-vetispirene, (±)-hinesol, and (±)-β-vetivone based on a Claisen rearrangement

The stereoselective total syntheses of (±)-α-vetispirene, (±)-hinesol, and (±)-β-vetivone were accomplished based on a Claisen rearrangement in an alkenyl bicyclic dihydropyran system. The most striking feature of this approach is that the Claisen rearrangement of bicyclic dihydropyran proceeds stereoselectively to provide a multi-functionalized spiro[4.5]decane, which is an efficient precursor for the synthesis of the vetivane sesquiterpenes.     

Synthesis of (±)-phthalascidin 650 analogue: new synthetic route to (±)-phthalascidin 622

A synthesis of functionalized phenolic α-amino-alcohol (±)-13 as synthetic precursor of the catechol tetrahydroisoquinoline structure of phthalascidin 650 is disclosed. Starting from 3-methylcatechol 5, eight steps of synthesis give rise to the synthesis of phenolic α-amino-alcohol (±)-13 in 27% overall yield. This synthetic strategy involves the elaboration of fully functionalized aromatic aldehyde 8 and its transformation into a phenolic α-amino-alcohol (±)-13, through a Knoevenagel condensation, simultaneous reduction of nitroketene and ester functions and hydrogenolysis of the benzyl protecting group. The pentacycle (±)-18 was obtained after four additional steps. The Pictet-Spengler cyclisation between the phenolic α-amino-alcohol (±)-13 and N-protected α-amino-aldehyde 4 allowed to obtain (1,3′)-bis-tetrahydroisoquinoline 14 with N-methylated and N-Fmoc removed. The last step was a Swern oxidation for allowing an intramolecular condensation.     

Synthesis of alkylated indolizidine alkaloids via Pummerer mediated cyclization: synthesis of (±)-indolizidine 167B, (±)-5-butylindolizidine and (±)-monomorine I

The syntheses of indolizidine alkaloids, i.e., (±)-coniceine, (±)-indolizidine 167B, (±)-5-butylindolizidine and (±)-monomorine I via Pummerer cyclization are described. The key step is the transformation of lactam sulfoxide to bicyclic lactam via the Pummerer cyclization.     

Total syntheses of (±)-cis- and (±)-trans-neocnidilides

Total syntheses of two antimicrobial natural products (±)-cis-neocnidilide and (±)-trans-neocnidilide starting from a readily preparable cyclohexa[b]-fused 5-oxabicyclo[2.1.1]hexane derivative are presented. The diastereomeric tetrahydrofuran tricarboxylate epimers obtained from a BF₃·OEt₂ promoted Grob-type fragmentation of the oxa-bicycle derivative were converted into title natural products by employing pyridinium dichromate/acetic anhydride mediated bis-oxidative cleavage reaction.     

Stereocontrolled total synthesis of (±)-pisiferol and (±)-pisiferal

The stereoselective total synthesis of (±)-pisiferol (1) and (±)-pisiferal (2) has been successfully accomplished using the trans-octahydrophenanthrene derivative 20 as a key intermediate. Intramolecular cyclisation of the diazoketone 15 followed by catalytic hydrogenation provided, stereoselectively, the keto-ester 17 which was converted into the acetate 20 through the intermediates 18 and 19.     

First total synthesis of (±)-puyanin and (±)- 4′-O-methylbonannione

A facile approach for the first total synthesis of two naturally occurring geranylated flavonoids, (±)-puyanin 1 and (±)-4′-O-methylbonannione 2 have been obtained with total yield 27% and 21%, respectively. The key steps were regioselective cyclization of geranylated tetrahydroxychalcone and regioselective geranylation of 2, 4, 6-trihydroxy- acetophenone.     

A new method of synthesising (±)-thalictroidine and (±)-hygrine

A new route to synthesise (±)-thalictroidine and (±)-hygrine by tandem S_N2-Micheal reaction is described.     

Synthesis of (±)-coerulescine and a formal synthesis of (±)-horsfiline

A straightforward synthesis of (±)-coerulescine and (±)-horsfiline has been established from 3-formyl-3-phenylpyrrolidine employing 4-hydroxypiperidine as the starting material. There are two remarkable steps for the synthesis of (±)-coerulescine and (±)-horsfiline. One is the rapid access to produce 3-formyl-3-phenylpyrrolidine by Lewis acid-catalyzed rearrangement of 3,4-dihydroxy-4-phenylpiperidine. The other key step is an intramolecular electrophilic cyclization from 3-benzylcarbamoyl-3-phenylpyrrolidine to the 3,3-spirocyclic 2-oxindole ring skeleton.     

Syntheses of (±)-thuriferic acid ethyl ester, its analogues and (±)-picropodophyllone

(±)-Thuriferic acid ethyl ester, its analogues as well as (±)-picropodophyllone have been prepared. The synthetic strategy is based on the utility of vicinal dianions derived from α-aroylsuccinic esters.     

Formal synthesis of (±)-brazilin and total synthesis of (±)-brazilane

A convergent synthesis towards (±)-brazilin and (±)-brazilane has been reported from 3,4-dimethoxy benzaldehyde in <15 reaction steps. Palladium(II)-catalysed intramolecular Friedel–Crafts cyclisation and Lewis acid supported intermolecular Friedel–Crafts alkylation reactions have been demonstrated. A tetracyclic substituted indane common key intermediate is employed to furnish the desired two molecules in good to excellent yield. Pd(OH)₂ has played a crucial role in the total synthesis of (±)-brazilane.     

Regioselective reduction of N-alkyl-3-sulfonyl glutarimides to δ-lactams. Formal synthesis of (±)-paroxetine and (±)-tacamonine

A convenient method for the preparation of 4- or 5-substituted 3-sulfonyl-δ-lactams via regioselective reduction of N-alkyl-3-sulfonyl glutarimides is described. Formal synthesis of (±)-paroxetine and (±)-tacamonine is also reported.     

Intramolecular ortho-arylation of phenols utilized in the synthesis of the aporphine alkaloids (±)-lirinidine and (±)-nuciferine

A palladium-mediated intramolecular phenol ortho-arylation reaction applied to the construction of aporphine alkaloids is reported. Most significantly, the efficiency of this transformation was enhanced by the utilization of trialkylphosphine (i.e. tricyclohexylphosphine) or trialkylphosphonium salts (i.e. di-tert-butylmethyl-phosphonium tetrafluoroborate) as co-catalysts in the presence of cesium carbonate. This methodology was employed in the syntheses of the aporphine alkaloids (±)-lirinidine and (±)-nuciferine.     

Total syntheses of (±)-lentiginosine and (±)-1-epi-lentiginosine from hexahydro-1H-indol-3-one

Total syntheses of (±)-lentiginosine 1 and (±)-1-epi-lentiginosine 2 were achieved efficiently from hexahydro-1H-indol-3-one 7.