A concise asymmetric total synthesis of (+)-brevisamide

A new protecting-group-free synthesis of the marine monocyclic ether (+)-brevisamide is reported. The enantioselective synthesis utilizes a key asymmetric Henry reaction and an Achmatowicz rearrangement for the formation of the tetrahydropyran ring. A penultimate Stille cross-coupling allows for an efficient installation of the conjugated (E,E)-diene side chain ultimately delivering (+)-brevisamide.     

Enantioselective total synthesis of aspidophytine

[structure: see text] An enantioselective total synthesis of aspidophytine is described. The indole fragment bearing a cis-alkene substituent was efficiently prepared through radical cyclization of a 2-alkenylphenylisocyanide followed by Sonogashira coupling of the generated 2-iodoindole derivative with a functionalized acetylene unit. After formation of the 11-membered cyclic amine, the aspidosperma skeleton and lactone ring were constructed to complete the total synthesis.     

A concise asymmetric synthesis of torcetrapib

Optically active torcetrapib was synthesized in seven steps from achiral precursors without the need for protecting groups, utilizing an enantioselective aza-Michael reaction to achieve asymmetry.     

New concise asymmetric total synthesis of (+)-desoxoprosophylline and prosophylline

Asymmetric total syntheses of (+)-desoxoprosophylline 1 and prosophylline 2 from 1-(α-furyl)-2-phenylmethoxy-N-tosylethylamine 3 were accomplished in 10 steps with an overall yield of 4% and in nine steps with an overall yield of 11%, respectively. The oxidation of 3 to dihydropyridone was used as the key step.     

A concise total synthesis of DL-histrionicotoxin

The synthesis of (+/-)-histrionicotoxin has been achieved in just nine steps using a two-directional synthesis strategy. Key reactions include a two-directional cross-metathesis, a tandem oxime formation/Michael addition/1,4-prototopic shift/[3 + 2]-cycloaddition cascade, a selective Z,Z-bisenyne formation, and a one-pot N-O and bischloroacetylene reduction.     

A concise total synthesis of salinosporamide A

A concise and straightforward 14-step total synthesis of (+/-)-salinosporamide A, based on a diastereoselective acid-catalysed intramolecular cyclisation of to the pyrrolidinone , and a regioselective reduction of the malonate derivative 8b to the aldehyde 9, is described.     

A concise total synthesis of naamidine A

[reaction: see text]. A total synthesis of naamidine A is reported. Key benefits of the described pathway include its brevity, its synthetic ease, and its flexibility with respect to the preparation of analogues. Formation of the 2-aminoimidazole core is achieved by condensation of the appropriate alpha-aminoketone with cyanamide.     

A concise total synthesis of bruceolline E

An efficient synthesis of bruceolline E was completed in three steps from the known ethyl indole-1-carboxylate (9d) in 60% overall yield, via a tandem acylation/Nazarov cyclization with 3,3-dimethyl acrylic acid followed by selenium dioxide oxidation to install the α-diketone functionality.     

A concise total synthesis of melithiazole C

A short and convergent synthesis of the myxobacterial antibiotic melithiazole C is described featuring a highly E-selective cross-metathesis as the key step.     

A short and concise asymmetric synthesis of hamigeran B

The interesting biological properties of the hamigerans wherein hamigeran B is a potent antiviral agent with low cytotoxicity to host cells make these deceptively simple looking structures challenging synthetic targets. A strategy to hamigeran B evolved wherein the three contiguous stereocenters are established ultimately from a Pd catalyzed asymmetric allylic alkylation (AAA). The latter involves an asymmetric allylation of a non-stabilized ketone enolate in 77 % yield and 93 % ee. By using this process, (S)-5-allyl-2-isopropyl-5-methyl-1-trifluoromethanesulfonyloxycyclopentene becomes available in four steps from 2-methylcyclopentanone. Introduction of the aryl unit by cross-coupling proceeded intermolecularly but failed intramolecularly. On the other hand, reductive removal of the triflate permitted a Heck reaction to effect intramolecular introduction of the aryl ring. The unusual conformational properties of this molecular architecture are revealed by the regioselectivity of the beta-hydrogen elimination in the Heck reaction and the diastereoselectivity of the reduction establishing the stereochemistry of the carbon bearing the isopropyl group. The successful route consists of 15 steps from 2-methylcyclopentanone and dimethylorcinol illustrating the efficiency of the route based upon the Pd AAA.     

A concise,asymmetric synthesis of tetramic acid derivatives

[reaction: see text] A simple, asymmetric synthesis of tetramic acid derivatives is described in this paper. The key step is a carbonyl transfer from carbonyldiimidazole (CDI) to alpha-diimines (I) to form N-alkyl-4-alkylamino-5-methylenepyrrol-2-ones (II). In turn, these compounds can be easily transformed into tetramic acid derivatives (III) in two additional steps.     

A concise asymmetric synthesis of (-)-rasfonin

A very efficient total synthesis of the apoptosis inducer (-)-rasfonin has been developed using CuBr/JosiPhos catalyzed iterative asymmetric conjugate addition of MeMgBr and Feringa's butenolide.     

A concise, convergent total synthesis of monocerin

A concise and convergent eight-step synthesis of the antifungal metabolite monocerin 1 is reported. The key step involves an allylsilane metathesis/aldehyde condensation sequence to establish the core 2,3,5-trisubstituted tetrahydrofuran. End-game approaches based around intramolecular Heck chemistry revealed an interesting example of formal 6-endo cyclisation, the origin of which was probed using model substrates. The synthesis was ultimately completed by a strategy involving stepwise oxidative cleavage of the C3-ethenyl substituent.     

A novel concise total synthesis of (+)-lentiginosine

A total synthesis of (+)-lentiginosine was achieved by using ethyl 3-(pyridin-2-yl)acrylate N-oxide as the starting material and an improved Sharpless asymmetric dihydroxylation as the key step.     

A concise stereoselective total synthesis of Botryolide B

The first total synthesis of Botryolide B is described from easily accessible starting materials. The synthetic strategy involves Jacobsen resolution, Sharpless epoxidation, Swern oxidation, Yamaguchi reaction, and ring closing metathesis (RCM).     

A concise total synthesis of (+)-okaramine C

The first total synthesis of (+)-okaramine C is described. Our previously described selenocyclisation-oxidative deselenation sequence was used to establish a 3a-hydroxy-pyrrolo[2,3-b]indole core, which was modified by selective epimerisation to the common pyrrolo[2,3-b]indole of the okaramines.     

A concise stereoselective total synthesis of (+)-artemisinin

A protective group free, concise, and stereoselective total synthesis of (+)-artemisinin, starting from readily available (R)-(+)-citronellal, is described. Asymmetric 1, 4-addition, Aldol condensation, Ene reaction, regioselective hydroboration are the key steps involved in the total synthesis of the target molecule.     

A concise first total synthesis of narceine imide

A concise and efficient total synthesis of alkaloid narceine imide is disclosed. The key steps are based upon the sequential construction of the isoindolinone template followed by metalation and coupling with an isoquinolinium salt. Subsequent E1cb elimination enables the creation of the arylmethylene unit with the concomitant formation of the dimethylaminoethyl chain and ultimate deprotection completes the synthesis of the natural product.