(-)-Cryptaustoline: its synthesis, revision of absolute stereochemistry, and mechanism of inversion of stereochemistry

Abstract

second sulfur atom. Further oxidation to the sulfenic acid derivative and lactonization would then yield thiotropocin. Experimental SectionMethods and Materials. NMR spectra were obtained at 400.13 or 250.13 MHz ( ) and 100.6 or 62.9 MHz (,3C). 'H/13C long-range HETCOSY spectral acquisition parameters: 20 000-Hz sweep width in the F2 dimension; 128 spectra (860 scans each) accumulated with a 2.0-s relaxation delay. Resolution was 9.766 Hz per point in the F2 dimension and 13.378 Hz per point in the Fj dimension. [l,2-l3C2]Phenylacetic acid (99 atom %), DL-[3-l3C]phenylalanine (99 atom %) and d-[U-i3C6]glucose (90 atom %) were purchased from ISOTEC, Inc. Thiotropocin (1) was converted to the p-bromobenzyl thioether derivative 2 as previously described.111 Fermentation of Pseudomonas CB-104. A loopful of cells from a cultivated slant was inoculated into 50 mL of seed medium in a 250-mL flask. The seed medium contained fructose (10 g), polypepton (BBL) (5 g), meat extract (Wako Pure Chemical Industries) (5 g), and NaCl (5 g) (pH 7.0) per liter. The inoculated seed culture was incubated at 28 °C for 2 days with reciprocal shaking at 100 rpm. The inoculum (0.8 mL) was transferred to 50 mL of the same seed medium and incubated at 24 °C for 1 day with 20 mL/min of aeration. The resulting culture (2.5 mL) was then transferred to 100 mL of production medium containing fructose (5 g) (sterilized separately), polypepton (0.5 g), meat extract (0.5 g), NaCl (0.5 g), and Na2S203 (0.05 g) (pH 7.0). The production medium was incubated at 24 °C for 36 h with 44 mL/min of aeration and 100-rpm agitation.Isolation and Purification of Thiotropocin. Cells from the above

Asymmetric Aza‐Henry Reaction of Indolenines Mediated by a Cinchona‐Alkaloid‐Thiourea Organocatalyst

“…As one of the representative five membered cyclic ( Z )‐imines, the readily prepared and storable 3 H ‐indoles (indolenines) have recently been recognized as a class of useful synthons for constructing chiral 2‐substituted indolines, the core moieties of many alkaloid natural products, such as (−)‐strychnine, cryptaustoline and (−)‐physostigmine as well as pharmaceuticals as exemplified by the angiotensin converting enzyme (ACE) inhibitor Pentopril (Figure )…”

The Palladium-Catalyzed Preparation of Condensed Tetracyclic Heterocycles and their Application to the Synthesis of rac-Mangochinine

“…10 The first total synthesis of dibenzopyrrocolines was reported by Kametani and co-workers, 11 who prepared racemic cryptaustoline (1) and cryptowoline (2) by an intramolecular aromatic nucleophilic substitution, while the absolute stereochemistry of 1 has been established as R-(-) by Meyers. 12 Kametani's process, carried out in the presence of a strong base, probably proceeds through a benzyne intermediate. This strategy was successfully extended by Kano also to the synthesis of indolo[2,1-a]benzazepine and quinolino[2,1-a]benzazepine derivatives.…”

Synthesis of indolo[2,1‐a]isoquinolines by CF3COOH‐induced cyclization

“…[ 1–5 ] Some of them have been shown to exhibit interesting biological activities [ 6‐12 ] including antileukemic and antitumor activities, [ 6‐8 ] nonsteroidal antiestrogen, [ 10 ] and anti‐tubulin activity. [ 11 ] Most of the reported methods for the synthesis of such alkaloids and related indolo[2,1‐ a ]isoquinolines [ 6‐59 ] involve the procedures ending up with the formation of the fused indole ring, such as benzyne method, [ 6–11 , 13–26 ] oxidative coupling, [ 27‐30 ] Bischler‐Napieralski cyclization, [ 31 ] photocyclization, [ 32 ] anionic cyclization, [ 33,34 ] radical cyclization, [ 34‐36 ] Pschorr cyclization, [ 37,38 ] Ni or Pd‐catalyzed intramolecular amination, [ 39,40 ] other metal‐catalyzed cycloaddition, [ 41‐50 ] and other methods. [ 12,51‐59 ] .…”