Ajmalicine, 19-epi

Akuammigine exists in solution at room temperature as an equilibrium mixture of trans-c/d and cis-c/d conformations [372] and [373], and at low temperatures the 13C NMR spectrum shows signals for both conformations. Comparison of the shifts of C(6) and C(14) in the room temperature spectrum (S 19-2 and 50-3) with those in the separate conformations permits an estimation of the position of equilibrium. (226) Iso-3-rauniticine [374] (228) is shown to adopt the trans-c/d conformation by its similar C(3), C(5), and C(6) shifts to those in [372]. For reference purposes, particularly in connection with the analysis of the 13C NMR spectra of the roxburghines (Section XII.K), 13C shifts for ajmalicine (normal series) and for 3-iso-19-epi-ajmalicine (pseudo series) are shown in [375] and [376]. (226)... 

The, 3C NMR spectra of roxburghine B, C, D, and E are summarized in [498]—[501 ]. (302) The, 3C shift assignments are aided by data on the ajmalicinoid alkaloids (Sections XII.D). Thus roxburghine D and E are related to 3-iso-19-epi-ajmalicine (pseudo series) and roxburghine C to ajmalicine (normal series). The angular methyl group in roxburghine E is... 

Biomimetic conversions reported51" on 7Vb,21-dehydrogeissoschizine include the formation of 17-hydroxydihydrocathenamine (64) on treatment with 2% aqueous hydrochloric acid and of isovallesiachotamine (65) in buffered solution at pH 4. Reduction (by NaBH4) of (64), followed by dehydration, affords 19-epi-ajmalicine (66) hence the configuration at C-19 is as depicted in (64). 19-epi-Ajmalicine (66) can also be obtained by the reaction of (61) with alumina, followed by reduction this may involve the intermediate formation of the fugitive dienamine (67), which can equilibrate with the (Z)-isomer of (61) before cyclization to the (19R) product (64) (Scheme 8).52... 

Ajmalicine, 19-epi-ajmalicine and tetrahydroalstonine are formed from 4,21-dehydrogeissoschizine via cathenamine (Fig. 2.9). The enzymatic synthesis of these corynanthe-type alkaloids has been investigated using C. roseus cell suspension cultures, and the enzymes involved have been reviewed by De Luca (1993) and Ziegler and Facchini (2008). Ajmalicine can be oxidized by POD to serpentine. This reaction may take in the vacuole. 

Syntheses of ( )-akuammigine, (+)-tetrahydroalstonine, ( )-ajmali-cine, (+)-3-iso-19-epiajmalicine, and the oxindoles (+ )-formosanine and ( )-isoformosanine, obtained by oxidative rearrangement of 3-iso-19-epi-ajmalicine, have been carried out starting with the key ketone (59). Scheme 7 illustrates how the product of either kinetic or thermodynamic control of the addition of malonate to this ketone can be used to synthesise d/e cts-alkaloids e.g., akuammigine (60)] or d/e trans-alkaloids [e.g., 3-iso-19-epi-ajmalicine (61)]. 

The formation of ajmalicine from the carbinolamine or cathenamine requires a reduction. Hemscheidt (217) and Stdckigt et al. (222) described an enzyme cathenamine reductase (CR), which used cathenamine as substrate and NADPH as cofactor, yielding ajmalicine and 19-epi-ajmalicine. Hemscheidt and Zenk (223) reported partial purification of an NADPH-dependent tetrahydroalstonine synthase (THAS) from C. roseus cell cultures. This enzyme only yields tetrahydroalstonine, and the substrate was the iminium form of cathenamine. The Km for this substrate is 62 /nAf. The molecular mass of the enzyme was estimated to be 81 kDa. 

Heteroyohimbine alkaloids. A group of indole alkaloids with the yohimbine structure but with an oxygen function in ring E (see formula under yohimbine) H. occur mainly in the Apocynaceae. Typical examples are ajmalicine (raubasine), 19-epi-ajmalicine, tetrahydroalstonine, rauniticine (all with the 3o-con-figuration), as well as serpentine and alstonine with an aromatic ring C. 

Scheme 18), the known intermediate (90) (Vol. 24, p. 313-4) was converted to (91), with base-catalysed epimerization at C-4, and then by reaction with tryptamine to (92). Bischler-Napieralski cyclization then led to (+)-19-epi-ajmalicine, and by including a Mitsunobu inversion at C-19, (-)-ajmalicine... 

C21H22N2O3, Mr 350.42, amorphous, [a]D -52° (CHCI3). 0 unstable, reactive alkaloid, existing as /d -immonium salts, isolated from Guettarda exi-mia (Rubiaceae) and synthesized enzymatically with enzymes from Catharanthus roseus cell suspension cultures C. plays a key role in the biosynthesis of monoterpenoid indole alkaloids, e.g., the hetero-yohimbine alkaloids such as ajmalicine, 19-epi-aj-malicine, and tetrahydroalstonine (see Alstonia alkaloids). 

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