Ring vinca alkaloids

The relative and predominant conformations of diastereomeric 14-hydroxy-( )-homoeburnanes 16 have been established by 1H- and 13C-NMR spectroscopy, indicating that previous assignments of C-12 and C-20 signals of trans-(D/E)-ring fused vinca alkaloids must be reversed (85JCS(P2)1319). 

VRLB is a semisynthetic derivative ofVLB (5 -noranhydrovinblastine), structurally distinguished from other members of its class by the modification of the cathar-anthine nucleus rather than the vindoline ring. This alteration is probably responsible for differences in its antitumor activity and tolerability profile compared with other vinca alkaloids [68]. VRLB is effective as monotherapy or in combination with a platinum derivative in patients with advanced NSCLC and advanced breast cancer [69,70]. Myelosuppression is the major dose-limiting toxicity. VRLB is administered weekly nadirs are usually reached within 14 days and patients recover within the next two weeks [71]. VRLB is also well absorbed orally. Oral and i.v. forms show similar interindividual variability, the same metabolism pattern, reproducible intrapatient blood exposure, and the same pharmacokinetic-pharmacodynamic relationship. Given at 60 mg/m /week for the first three administrations and then increased to 80 mg/m /week it achieved the same efficacy as i.v. VRLB (30 mg/m ) in terms of progression-free survival, overall survival, and objective response [70]. 

VInorelbine Tartrate. Vinorcibine tartrate. Navelbinc. is a new scmisynthctic vinca alkaloid derived from vinblastine by loss of one carbon from ring C and dehydration in ring D. both in the catharanthine moiety. It is named 3. 4 -didehydro-4 -dcoxy-C -norvincalcukoblastinc. Navcibine is supplied in vials containing 10 mg/mL of solution in a volume of I mL of Water for Injection or 10 mg/mL of solution in a volume of 5 mL of Water for Injection. Unopened vials are stable at room temperature fur up to 72 hours. It is diluted to a concentration of 0.5 In 2 mg/mL with 0.9% Sodium Chloride Injection or 5% Dextrose Injection for intravenous infusion or slow intravenous push administration. 

The female client diagnosed with Hodgkin s disease is prescribed vincristine (Oncovin), a vinca alkaloid. Since the last treatment the client complains that she cannot wear her rings or most of her shoes because of weight gain. Which action should the nurse take first ... 

Boger has shown that tether lengths that provide a 5-6 ring system after cyclization are ideal for the synthesis of vinca alkaloids such as vindoline [78], Adjustment of the length of the tether connecting the indole to oxadiazole, or the dienophUe to oxadiazole, are tolerated. As expected, varying tether lengths have effects on the reaction rates and yields of cycloaddition products 161 (Scheme 45). 

Kalaus G, Vago I et al (1995) Synthesis of vinca alkaloids and related compounds. 776. Synthesis and ring transformatitnis of compounds with the aspidospermane- and D-noraspidospermane skeletrai. A formal synthesis of (+-)-12-demethoxy-N(l)-acetylcylin-drocarine. Nat Prod Lett 7 197-204... 

Vago I, Kalaus G et al (2001) Synthesis of vinca alkaloids and related compounds. 95. Attempted build-up of the aspidospermidine skeleton by [4+2] cycloaddition. Some unexpected reactions, and formation of a new ring system. Heterocycles 55 873-880... 

A concise synthesis of biologically important Vinca alkaloid ( )-3H-epivincamine was accomplished. A central step in the synthesis consists of rhodium-catalyzed intramolecular [3-l-2]-cycloaddition of a-diazo amide 223 which provides the cycloadduct 224, which has the core skeleton of the natural product, in excellent yield with complete diastereoselectivity (Scheme 70). Further, a reductive ring opening of the cyclo adduct followed by a decar-boethoxylation reaction and a base-induced keto-amide ring contraction reaction furnished ( )-3H -epivincamine (225) [171]. 

Two new zwitterionic alkaloids with a 5,6-dihydroindolo[2,3-a]quinolizine ring system have been isolated from Vinca major L. var. elegantissima Hort (13). The structures of vincarpine (4) and dihydrovincarpine (5) have been determined on the basis of their spectral data and via some derivatives obtained by either catalytic or hydride reduction. Interestingly, the H-NMR spectrum of vincarpine in TFA solution corresponds to structure 6 derived by lactonization of 4 in the presence of acid. 

Sewarine, from Rhazya stricta, was shown to be 10-hydroxyakuammicine (66a) by spectral comparison with akuammicine (66b) and with other a ring oxygenated indole alkaloids. " Preakuammicine (67a), an isomer of precondylocarpine (67b), has been isolated from young Vinca rosea seedlings. " The retroaldol loss of formaldehyde and the formation of akuammicine was base catalysed. Boro-hydride reduction, as well as causing some retroaldolisation, gave rise to stemmadenine (65). 

Dopke et al. (77) obtained an interesting seco ring C Aspidosperma alkaloid from Vinca minor L. to which they gave the name vincatine (163). 

This amorphous base (C23H28N2O6) was isolated in small amounts from the aerial parts of Vinca major. Its mass spectrum was superimpos-able upon that of carapanaubine and the UV-, IR-, and NMR-data agreed well with a structure of the type XXXIIa-c. The NMR-spectrum of the alkaloid further indicated a pair of o-hydrogen atoms in the aromatic ring. However, a decision could not be made among the three possible structures (31). 

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