Über eine einfache Synthese der Yohimbinalkaloide

Abstract

~ Das zur Synthese DIE-trans-und D/E-c.i.werkniipfter Yohimbinalkaloide geeignete Zwischenprodukt 2a wird aus 1 adurch Dieckrticirir~-Ko~idensation rnit 63% Ausbeute erhalten. AnschlieDende Hydrierung des Enonsystems ergibt Yohimbin (Xa) und a-Yohimbin (8b). Mit Basen wird 2a zu 3 a umgewandelt. aus dem iiber 6 a und 7a Alloyohimbin. a-Yohimbin. 3-Epi-a-yohimbin und die in der Natur nicht vorkommenden Isomeren 8e. g. h und i mit D/E-cis-Verknupfung als Racemate erhalten werden. A Symple Synthesis of Yohimbine AlkaloidsThe methyl ester 2a. a useful intermediate for the preparation of DIE-trans-and ci5-anellated yohimbine alkaloids, is obtained from 1 a by Dieckmcrnn-condensation in 63 yield. Subsequent hydrogenation of the enone-system provides yohimbine (8a) and p-yohimbine (8b). On base treatment 2 a rearranges to 3 a which in turn is converted via 6 a and 7 a to the racemic. DIE-cisanellated alkaloids alloyohimbine. a-yohimbine. 3-epi-a-yohimbine as well as the nonnaturally occurring isomers 8e. g. h. and i.Wir berichteten friiher iiber die Synthese von Yohimbin (8a) und P-Yohimbin (8b)'). iiber die Herstellung von Alkaloiden rnit Allo-und Epi-alloyohimbingerust sowie uber die Revision der Alloyohimbin-Struktur (8d) 2, '). Mit der Synthese von Verbindungen rnit Yohimbingerust befafiten sich in der letzten Zeit auch andere Forschergruppen 4-6).Im folgenden berichten wir iiber eine einfache Synthese von DIE-trunsund DIE-cisanellierten Yohimbinalkaloiden aus einer gemeinsamen Vorstufe. Der gemischte ungesattigte Ester 1 a. dessen Analoga rnit Benzo[a]chinolizin-Geriist bereits eingehend studiert wurden ' I , erschien fur diesen Zweck geeignet. Mit dem Diester 1 a kann der Dieckmum-Ringschlu0 rnit der erforderlichen Regioselektivitat verwirklicht werden').

Synthesis of yohimbines. 4. Synthesis of (.+-.)-3-epi-.alpha.-yohimbine and (.+-.)-3,17-epi-.alpha.-yohimbine. Carbon-13 NMR investigation of yohimbine stereoisomers

“…Isorauhimbine isolated by Hofmann1 from Rauwolfia serpentina Benth has been known since 1954 and was later found to be identical with 3-epi-a-yohimbine (l)3 isolated by Schlittler.2 In the past 2 decades several total sytheses leading to yohimbines were developed,4 5"7 but none of them yielded isorauhimbine (1), including our attempt via reduction of 3-epi-alloyohimbinone (2). 8 In previous parts of this series5"8 we reported on the synthesis of nine isomeric yohimbines with natural and nonnatural stereochemistry. For completion of this work, we now report on the transformation of racemic alioand epi-alloyohimbine stereoisomers 5, 7, and 9 (synthesized earlier in our laboratories5-9) into (±)-3-ept-«-yohimbine (1) by means of C (3) and C( 16) epimerizations, respectively.…”

“…The physical and spectral (IR, 13C NMR, and mass spectral) properties of the synthetic product were identical with those of the natural To complete our work on the synthesis of yohimbine stereoisomers having an epi-allo skeleton, we have prepared the fourth unknown representative, the racemic 3,17epi-a-yohimbine (3). 3 was obtained also from the corresponding alio isomer,717-epi-a-yohimbine (8) similarly by dehydrogenation with mercury(II) acetate and subsequent reduction with zinc in acetic acid The values are in parts per million from internal Me4Si. Data for 1, 7, 9, 12, 13, and 15 are taken from ref 11. b In CDClj solution.…”

Modifications in the upper or Velbenamine Part of the Vinca Alkaloids have Major Implications for Tubulin Interacting Activities

“…It should be mentioned that only 17-nitrovinblastine 13 (thus substituted in the vindoline moeity) was isolated when vinblastine 1 was treated under the same conditions (Fig. (4)) [11]. Overall, none of these A'-modified derivatives exhibited any major improvement in terms of their antitumour activities, and no further studies have been reported so far.…”

Synthesis of Reserpine‐type Alkaloids, I. An Approach to the Preparation of Tetracyclic Key Intermediates

“…C 38.61 H 6.48 N 3.75 Found C 38.48 H 6.39 N 3.61 Formation of I- (5-methoxycarbonyl-2-oxotetrahydrofuran-3-y~-N,N, N-trimethylmethanaminium iodide (10) and 11: The former reaction sequence was carried out starting from 8 c (20 g, 72 mmol), using dimethylamine hydrochloride (6.2 g, 77 mmol) and 37-07" aqueous formaldehyde (7.5 ml) for the Mannich reaction. After workup and re-esterification the final reaction mixture yielded the easily decomposing ester 11 (3.5 C,,H2,2,3,4,6,7,12,…”