Total synthesis of (+/-)-cytisine

[reaction:see text] The nicotine partial agonist cytisine was prepared in five steps featuring an "in situ" Stille or Suzuki biaryl pyridine coupling. Differentiation of the pyridyl rings was accomplished via selective benzylation and then reduction of a pyridinium ring. The penultimate diazabicyclo[3.3.1]nonane intermediate was obtained with high diastereoselectivity. A similar sequence has been employed for the synthesis of novel derivative 9-methoxycytisine.     

A short synthesis of (+/-)-cytisine

The synthesis of racemic cytisine has been completed using (i)N-selective alkylation of 6-bromopyridone with bromide and (ii) Pd(0) mediated intramolecular alpha-arylation of lactam as key steps to achieve rapid assembly of the tricyclic core skeleton of the lupin alkaloids.     

Total synthesis of (+/-)-mycothiazole and formal enantioselective approach

[Reaction: see text] A total synthesis of (+/-)-mycothiazole and a formal enantioselective approach have been achieved from 2,4-dibromothiazole. A chain extension of a homoallylic alcohol proceeding through an unsaturated sultone intermediate, generated by ring-closing metathesis, was used as a key step for the elaboration of the conjugated (Z)-dienol moiety.     

Total synthesis of (+/-)-cytisine via the intramolecular heck cyclization of activated N-alkyl glutarimides

[reaction:see text] A synthesis of racemic cytisine 1 has been developed utilizing an intramolecular Heck cyclization to prepare the bridged tricyclic intermediate 2. The cyclization employs activated glutarimide-derived ketene aminals 3 (X = P(O)OEt(2) or SO(2)CF(3)) and represents the first use of such intermediates in metal-catalyzed processes.     

Total synthesis of (S)-(+)-tylophorine via enantioselective intramolecular alkene carboamination

The enantioselective synthesis of (S)-(+)-tylophorine, a potent cancer cell growth inhibitor, has been accomplished in eight steps from commercially available 3,4-dimethoxybenzyl alcohol. A copper (II)-catalyzed enantioselective intramolecular alkene carboamination was employed as the key step to construct the chiral indolizidine ring.     

Concise synthesis of (+/-)-cytisine via lithiation of N-Boc-bispidine

[reaction: see text] (+/-)-Cytisine has been synthesized in 19% overall yield via a six-step approach from commercially available materials. Key features of this new strategy are as follows: (i) initial construction of the bispidine core, (ii) lithiation-transmetalation-allylation of an N-Boc-bispidine, and (iii) a Pd/C-mediated dihydropyridone oxidation-N-debenzylation process.     

Divergent enantioselective synthesis of (-)-galanthamine and (-)-morphine

An efficient divergent synthetic strategy for the synthesis of the opiate and amaryllidaceae alkaloids emerges by employing a Pd-catalyzed asymmetric allylic alkylation (AAA) to set the stereochemistry. Three generations of syntheses of galanthamine are discussed in detail with particular focus on the scope of the palladium-catalyzed AAA reactions and intramolecular Heck reactions. The pivotal tricyclic intermediate is available in six steps from 2-bromovanillin and the monoester of methyl 6-hydroxycyclohexene-1-carboxylate. This intermediate requires only two steps to convert to (-)-galanthamine. Using a Heck vinylation, we found that the fourth ring of codeine/morphine could be formed. The final ring formation involves a novel visible light-promoted hydroamination. Thus, six steps are required to convert the pivotal tricyclic intermediate into codeine, which has been demethylated in high yield to morphine.     

An enantioselective formal synthesis of (-)-thujopsene

Dihydromayurone (3), a key intermediate to synthesize (-)-thujopsene (1), was efficient enantiocontrolled synthesized from ( )-dihydrocarvone through 9 steps in an overall yield of 19.3%. The key step was the Simmons-Smith reaction.     

First enantioselective total synthesis of (-)-Centrolobine

[structure: see text] The first enantioselective total synthesis of (-)-Centrolobine is described. The key reaction is the synthesis of the cis-disubstituted tetrahydropyran framework by intramolecular cyclization of the enantiopure hydroxyketone 3 with Et3SiH and TMSOTf. The stereoselective reduction of the beta-ketosulfoxide 4 is the source of chirality. Revision of the absolute configuration of (-)-Centrolobine is proposed.     

First enantioselective total synthesis of (-)-tejedine

[structure: see text] The first enantioselective total synthesis of (-)-tejedine (1) is reported. Tejedine is a seco-bisbenzyltetrahydroisoquinoline isolated in 1998 as a minor component from Berberis vulgaris. The synthesis was achieved using a strategy employing four key steps, including a chiral auxiliary-assisted diastereoselective Bischler-Napieralski cyclization.     

An enantioselective formal synthesis of （-）-thujopsene

Dihydromayurone （3）, a key intermediate to synthesize （-）-thujopsene （1）, was efficient enantiocontrolled synthesized from （＋）-dihydrocarvone through 9 steps in an overall yield of 19.3%. The key step was the Simmons-Smith reaction.     

An efficient enantioselective synthesis of (S)-(-)-acromelobic acid

[reaction: see text] A highly efficient enantioselective synthesis of (S)-(-)-acromelobic acid (1) was achieved via asymmetric hydrogenation of dehydroamino acid derivative (3) using (R,R)-[Rh(DIPAMP)(COD)]BF(4) catalyst followed by removal of protective groups in >98% ee and good over all yield. The key intermediate (3) was prepared from the commercially available citrazinic acid (4) in six steps.     

Total synthesis of (-)-ratjadone

[reaction in text] A convergent asymmetric synthesis of (-)-ratjadone (1) has been achieved, confirming the assignments of stereochemistry for the naturally occurring antifungal metabolite.     

Total synthesis of (-)-dysiherbaine

The enantioselective synthesis of (-)-dysiherbaine (1) has been established with efficiency via a unique synthetic strategy involving the desymmetrization of 2-substituted glycerol to install a quaternary chiral carbon, which induces further stereochemistry in the bicyclic perhydrofuropyran through mercuriocyclization and epoxidation.     

Total synthesis of (-)-dendrobine

Cascading to alkaloids: An 18-step total synthesis of (-)-dendrobine is based on a reaction cascade with a key amine group (see scheme, Bn=benzyl). The amine is the initiator of the cascade and provides an efficient method for installing the stereocenters at C11 and C3. The overall transformation occurs stereoselectively only when the conversion is carried out without the isolation of intermediates.     

Total synthesis of (-)-raumacline

The total synthesis of (-)-raumacline from L-tryptophan was achieved, featuring a cis-specific Pictet-Spengler reaction, a stereoselective Dieckmann cyclization, and an epimerization step that allowed complete stereocontrol of five chiral centres.