General Approach for the Synthesis of Indole Alkaloids via the Asymmetric Pictet−Spengler Reaction:  First Enantiospecific Total Synthesis of (−)-Corynantheidine as Well as the Enantiospecific Total Synthesis of (−)-Corynantheidol, (−)-Geissoschizol, and (+)-Geissoschizine

The Double‐Bond Configuration of Corynanthean Alkaloids and Its Impact on Monoterpenoid Indole Alkaloid Biosynthesis

“…The trans-quinolizidine system was determinedb ym eans of the following seven criteria ( Figure 5): a) The presence of Bohlmann bands in the IR spectrum of the trans-quinolizidine; [15] b) consistently lower chemical shifts of the H3, H5 (axial), and H21 (axial) protons in the trans-quinolizidine; [16] c) two trans diaxial (anti)c oupling constantsf or the (H a )14 atom and two gauche-like coupling constantsf or the (H b )14 atom (by contrast, the cis-quinolizidine displays exclusively gauche interactions at the (H ab )14 atom); [17] d) the signal pattern of protonH 3 is "doublet-like" with J > 10 Hz, which corresponds to one anti and one very small gauche interaction (J % 0Hz), in the transquinolizidine (as opposed to a" triplet-like"s ignal of protonH 3 in the cis-quinolizidine, which corresponds to two gauche interactions with the same coupling constant, J 1 = J 2 ); [16] e) consistently higherc hemical shifts in the 13 CNMR spectrumf or the C3, 6, 14, 15, and 21 atoms in the trans-quinolizidine (Dd = 3-13 ppm); [2b, 18] f) the reactivity in the salt formation with methyl iodide: cis-quinolizidines are quarternized smoothly,w hereas trans-quinolizidines react reluctantly; [19] and g) the presence of the following characteristicN OE signals in the trans-quinolizidine:H 16-19 and H3-21.…”

“…Criterion e: Ac omparison of the 13 CNMR spectra of 9 and 7 reveals significant differences for the C3, 6, 14, 15, and 21 atoms. The Z isomer 9 displays higherc hemical shifts at these carbon atoms, which corresponds to a trans conformation of the quinolizidine system (Table 1).…”

“…This effecti sm issing in the Z derivatives, whichleaves the system in the trans-quinolizidine conformation and prohibits secondary cyclizations; hence,n oa lkaloids with aC 19-C20 Z-configured double bond occur.T o probe our hypothesis, we carriedo ut detailed conformation analyses of compounds 1, 2,and 6-9 (Figure 2). [13] …”

The Chiral Pool in the Pictet–Spengler Reaction for the Synthesis of β-Carbolines

“…However, under these conditions the racemization of the products was possible [22]. By this methodology, besides the application of Cook's group to the preparation of natural products [18,[23][24][25][26][27][28], a new class of inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase B was synthesized by Waldmann and co-workers [29].…”

Enantioselective Syntheses of Corynanthe Alkaloids by Chiral Brønsted Acid and Palladium Catalysis

“…[4] Over the years several racemic and partial enantioselective syntheses of corynantheidine 1 and its C20-epimer (+)-dihydrocorynantheine 3 have been published, but only a few enantioselective total syntheses have appeared. [6] (+)-Corynantheine 2 contains a C20-vinyl substituent, and although it is the most frequently described member of the corynanthe family, no enantioselective total synthesis of 2 has been reported yet. Most of the existing corynanthe syntheses share tryptophan as the chiral source in a Pictet-Spengler reaction thus requiring additional steps to remove the carboxyl group.…”