Related Alkaloids

As far back as 1915 Clewer and co-workers investigated the tubers of Gloriosa superba L. (Liliaceae) obtained from Sri Lanka for alkaloids 

Lycopodine was isolated by Bodeker in 1881 (I) but its molecular formula, C16H25NO, w as not established until 1938 when it was isolated from L. davatum and characterized by Achmatowicz and Uzieblo (3). 

In the same communication MacLean et al. (79) described the reaction of lycopodine with cyanogen bromide. The products of this reaction, a- and (8-bromocyanolycopodine, proved to be key intermediates in the development of the structure of the alkaloid. In a study of the reactions of the isomeric bromocyanamides the author and his students 17, 41, 80-82) established the peripheral structure of lycopodine. The information obtained in their studies in conjunction with the dehydrogenation data of Marion and Manske (78) allowed the assignment of structure XLVIII to lycopodine in 1960. Since the lycopodine skeleton is found in the majority of Lycopodium alkaloids of known structure the elucidation of the structure of lycopodine will be treated here in considerable detail. 

Hydrogenolysis of XLIX over Pd-CaCOa in alkaline medium gave -cyanolycopodine LIII (79). Modified Kuhn-Roth oxidation of the alcohol derived by borohydride reduction of LIII yielded a mixture of butyric, propionic, and acetic acids whereas similar treatment of lyco-podine gave only acetic acid. Clearly a w-propyl group is present in LIII. Moreover, the relatively high yield of butyric acid, 24 % of the mixture, suggested that C-12 is not quaternary as it is in annotinine (41). 

Attempts to carry out a similar sequence of reactions on j8-bromo-cyanolycopodine LIV were thwarted for a long time by the tendency of this compound to eliminate hydrogen bromide. Treatment with potassium acetate in methanol, amines, and other bases always led to the same nonketonic, very unreactive compound, which was eventually shown to be the enol ether LV 41). With silver acetate in benzene, however, LIV yielded a mixture of LV and an acetoxy compound in an approximate ratio of 3 1. Treatment of the acetate in the same sequence of reactions used in the a-series gave the carboxylic acid LVI. When LVI was treated with sodium borohydride and the acidified reaction mixture extracted into chloroform a neutral compound was isolated. In its IR-spectrum it had 1743 cm in Nujol which shifted to 1761 cm i in chloroform solution, but there was no absorption in the hydroxyl region. The IR-speetrum and the elemental analysis were in agreement with the lactone structure LVII. When this work was carried out, however, the IR-evidence alone was not sufficient to differentiate between a y- and a S-lactone ( Sf). 

The ketoacid LVI was converted by the method used in the a-series to lactam LVIII which had v ax 1700 and 1626 cm, attributed to ketone and lactam functions, respectively. Treatment with lithium aluminum hydride converted LVIII to dihydrolycopodine LII showing that no change in carbon skeleton had occurred in the formation of LVIII. The IR-data showed that ring B like ring A is six-membered or larger 41). 

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Caffeine. About 3% by weight of the roasted coffee bean is caffeine (16). The second U.S. Department of Agriculture world coffee crop estimate for 1988—1989 was 4.24 x 10 kg (93.3 million 100-lb bags) (102). World coffee consumption was predicted to rise in the foreseeable future at the rate of 1—2% per year and thus the total amount of caffeine and related alkaloids ingested from this source can also be expected to increase. Caffeine and related bases (eg, theophylline) are also found in various teas but, because most of the major producers (India, China, etc) export relatively Htfle of thek crops and keep most for domestic consumption, accurate figures on year-to-year production are more difficult to obtain. Nevertheless, these crops are of significant economic import (103). 

At this writing anticholinergic agents are not widely used for the symptomatic treatment of asthma, although compounds such as atropine [51 -55-8] C17H23NO3, (18) have been used for centuries (111). Inhalation of the smoke produced by burning herbal mixtures, such as Datura Stramonium provided bronchodilation and rehef from some of the symptoms of asthma. The major active component in these preparations was atropine or other closely related alkaloids (qv). 

Quinazoline alkaloids are found in at least six botanical families of which the Rutaceae are the most important in this respect. Thus, arborine was isolated from Glycosmis arborea in 1952 and in the following year appeared its structure (990) and synthesis by thermal cyclization of the phenylacetyl derivative (989) of (V-methylanthranilamide (53JCS3337>. The same plant material yields three related alkaloids, glycosmicine (991), glycorine (992) and glycosminine (993) (63T1011>. 

There are several alkaloids in the structure of which are both quinazoline and indole nuclei. Evodiamine (1001 R = H) and rutaecarpine (1002) were both isolated from the seeds of Evodia rutaecarpa about 1916 and synthesized in 1927. They were found subsequently to occur also in Xanthoxylum rhetsa, which in addition yielded rhetsinine (1001 R = OH) (59T(7)257). The plant Hortia arborea afforded two more related alkaloids, hor-tiacine and hortiamine, each characterized by a methoxy group in the benzene ring of the indole portion (60JA5187). 

For convenience of comparison the characters of these nine closely related alkaloids are summarised in the following table —... 

This review is an attempt to collect under one heading and to present in a systematic manner the large body of work which deals with the chemistry of the carboline ring systems. Some three hundred papers in this field have been published during the last decade, more than twice as many as appeared during the preceding fifty years. The renewed interest in the chemistry of the carbolines is due in no small measure to the discovery of serotonin and to the recent developments in the chemistry and pharmacology of the Rauwolfia and related alkaloids. 

Isolation, synthesis, and possible mechanism of action of anticancer alkaloid camphotecin and related alkaloids 99YGK181. 

The Reissert method15—conversion of an isoquinoline to a 2-benzoyl-1,2-dihydroisoquinaldonitrile (Reissert compound), alkylation, and hydrolysis—has enjoyed wide success in the synthesis of benzyliso-quinoline and related alkaloids.16,17 In particular, aporphines are prepared conveniently by converting isoquinolines to I-(o-nitrobcnzyl)-isoquinolines via a Reissert sequence, followed by A7-alkylation, reduction, and Pschorr cyclization.17... 

Heckrodt TJ, Mulzer J (2005) Marine Natural Products from Pseudopterogorgia Elisabe-thae Structures, Biosynthesis, Pharmacology and Total Synthesis. 244 1-41 Heinmaa I, see Samoson A (2005) 246 15-31 Helm L,see Toth E (2002) 221 61-101 Helmboldt H, see Hiersemann M (2005) 243 73-136 Hemscheidt T (2000) Tropane and Related Alkaloids. 209 175-206... 

Iridoids and their related alkaloids are widely spread in angiosperms and are found in 13 orders and 70 families including Rutales, Buxales, Hamamelidales, Comales, Loasales, Gentianales, etc. Important iridoids are loganin, found in high amounts in Strychnos nux-vomica and in Catharanthus roseus, and secologanin found especially in Caprifoliaceae. 

The biogenetic approach, which is a linear approach, is based on the stepwise disconnection of 18 into a series of biogenetically related alkaloid precursors. The precursors are usually built up in the actual synthesis with the C10 indole chromophore attached from the beginning and with stepwise modification of the alicyclic portion of the molecule later on. An example of this kind of approach is illustrated in Scheme 14 (43). 3(R)-Vobasinediol (58) is... 

Scheme 1. Biosynthetic relationships between protoberberines and related alkaloids.

In conclusion, although the Stevens rearrangement of a tetrahydroproto-berberine metho salt readily afforded a spirobenzylisoquinoline skeleton, there exist no reports on synthesis of functionalized spirobenzylisoquinolines or related alkaloids using this method. 

Scheme 94. Synthesis of chilenine (380) and its conversion to related alkaloids. Reagents a, aq NH3 b, py-HCl, py c, Zn, HCl-AcOH d, NaBH4 e, Mel, MeOH f, AcOH g, NaOH, aq MeOH h, CF3COOH.

Ring D inversion seems to be a crucial step in biogenetic transformations of protoberberines to related alkaloids such as rhoeadine, retroprotoberberine, spirobenzylisoquinoline, and indenobenzazepine alkaloids. 8,14-Cyclober-bin-13-ol 478 derived from berberine (15) was successively treated with ethyl chloroformate, silver nitrate, and pyridinium dichromate (PDC) in dimethyl-formamide to give the keto oxazolidinone 479 (Scheme 98). Heating of 479 with 10% aqueous sodium hydroxide in ethanol effected hydrolysis, retro-aldol reaction, cyclization, and dehydration to provide successfully the... 

During the enantiospecihc total synthesis of ajmalin-related alkaloids, (-)-suaveoline and (-)-raumacline, N-debenzylation of the hydrochloride salt of the alkaloids was performed with 10% Pd/C (0.12 mol Pd/mol compound) in absolute EtOH at room temperature and 1 atm of hydrogen for 1 or 2 hours. When this catalytic debenzylation was performed, however, using 10% Pd/C (0.28 mol Pd/mol compound) in MeOH for 5 hours, N-methyl derivatives were produced in good yield (Scheme 4.91).339,340... 

Hemscheidt T (2000) Tropane and Related Alkaloids. 209 175-206 Hendrickson DN, Pierpont CG (2004) Valence Tautomeric Transition Metal Complexes. 234 63-95... 

For biogenetic studies of the Strychnos alkaloids, see (a) Bisset NG (1980) In Phillipson JD, Zenk MH (eds) Indole and biogenetically related alkaloids, Academic, London, pp 27-61 (b) Kisakiirek MV, Leeuwenberg AJM, Hesse M (1983) In Pelletier SW (ed) Alkaloids chemical and biological perspectives, vol 1. Wiley, New York, NY, pp 211-376... 

Two other closely related alkaloids from the root bark of T. divaricata were studied by Rastogi et al. and shown to be isomeric with 3-oxocoronaridine (99). The first compound (MP 272-275°C, [a]D -10.7°) displayed in its H-NMR spectrum an AB system centered at 3.91 ppm (/ = 15 Hz). This was indicative of... 

Two new pseudotabersonine-related alkaloids were isolated by Husson et al. from the stem bark of T. albiflora from French Guiana (29) and characterized as (20/ )-18,19-dihydroxypseudovincadifformine (166, C2iH26N204, MP 190°C, [a]D +264°) and 19-hydroxy-20-epipandoline (167, C21H26N204, MP 204°C, [a]D +511°. Both compounds exhibited similar UV maxima attributed to a (3-anilinoacrylic chromophore, and their mass spectra showed, in addition to a molecular ion at m/z 370, a base peak at m/z 156 formed by retro-Diels-Alder fragmentation in ring C, followed by C-6—C-5 bond cleavage. 

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