The first enantioselective total syntheses of indolealk aloids of the condylocarpine type are reported. (+)-Condylocarpine, (+)-isocondylocarpine, and (+)-tubotaiwine were prepared in high enantiomeric purity (er >99:1) from (1 S,5 R) -hexahydro-1,5-methano-1 H-azocino[4,3 -b]indole-12-one 7b by way of five or six isolated intermediates.The hexahydro-1,5-methano-1H-azocino [4,3-b]indole ring system 1 is a major fragment of Strychnos alkaloids of the strychnan and aspidopermatan types (e.g., 2-4, Figure 1) and the ring system of indole alkaloids of the uleine group (e.g., 5, Figure 1).1 During our recent total synthesis of the structurally unique indole alkaloid (−)-actinophyllic acid, we developed a concise synthesis of the hexahydro-1,5-methano-1H-azocino [4,3-b]indole ring system.2 , 3 A central step in this synthesis is an iron(III)-promoted intramolecular oxidative coupling of malonate and ketone enolates generated from indole piperidones 6 to deliver hexahydro-1,5-methano-1H-azocino [4,3-b]indole-12-ones 7 (eq 1). Ketone (1S,5R)-7b was prepared in enantioenriched form (er = 95:5) in 26% overall yield from 4-(tertbutoxycarbonylamino)butyric acid by way of six isolated intermediates.2 , 4 Herein we report the use of tetracyclic intermediate (1S,5R)-7b for the enantioselective synthesis of three representative members of the condylocarpine subtype of the aspidospermatan group of alkaloids.5 , 6(1) leoverma@uci.edu. Supporting Information Available: Experimental details and copies of 1 H and 13 C NMR spectra of new compounds (PDF); CIF files for compounds (±)-20 and (±)-iii. This material is available free of charge via the Internet at http://pubs.acs.org. Transformation of hexahydro-1,5-methano-1H-azocino [4,3-b]indole-12-ones 7 to the condylocarpine skeleton requires introduction of a two-carbon unit at C12, installation of a two-carbon bridge between C11b and N2, and dealkoxycarboxylation of the malonate unit. Our early exploratory investigations were carried out in the racemic series and focused on elaboration of C12 and N2. Several observations made during these studies provided essential insight into the chemical reactivity of the hexahydro-1,5-methano-1H-azocino [4,3-b]indole ring system (Scheme 1). Wittig reaction of ketone (±)-7a with ethylidenetriphenylphosphorane delivered ethylidene derivative (±)-8 as a single stereoisomer in 73% yield, with the Z configuration of the double bond being readily secured by 1 H NMR NOE analysis. To our surprise, this product was extremely acid sensitive. For example, (±)-8 rearranged to hexahydro-6H-pyrido [4,3-b]carbazole isomer 9 when stored in CDCl 3 for several days, or within 2 h at room temperature in the presence of 10 mol % of DCl (0.004 M). Related instability was observed with hexahydro-1,5-methano-1H-azocino [4,3-b]indole-12-one (±)-7b, which when exposed in CDCl 3 to 0.15 M DCl for 2 h gave dihydropyrrolo[3,2-b]carbazole 10 in 55% yield.7 Under stronger acidic conditions (neat TFA), ketone (±)-7b yielded 3-hydroxycarbazole-1-carboxylic acid 11 as t...

A useful transformation in enantioselective synthesis: (−)‐Sparteine‐assisted lithiation of the propargylic 1‐thiocarbamate 1 (Cb=CONiPr2) forms the enantiomerically and diastereomerically pure lithium (−)‐sparteine complex 2. Its solid‐state structure and application in the asymmetric synthesis of highly enantioenriched 1‐thioallenes 3 were investigated.

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Our results show that pectus carinatum is efficiently treated with a customized brace therapy within 7 to 12 months. Best correction can be achieved in children and young adolescents. Daily brace-wearing time should be above 14 hours, ideally 24 hours. Duration of the treatment should be around 1 year. Treatment results correlate directly with the cooperation of the patients.