Simple pyrrolidines

ODC = ornithine decarboxylase PMT = putrescine methyltransferase MPO = methylputrescine oxidase OCT = ornithine carbamoyltransferase ADC = arginine decarboxylase AIH = agmatine iminohydrolase CPA =/v-carbaiTioylputrescine amidohydroiase SAM = S-adenosyl-methionine 

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Besides piperidine alkaloids, a total of 19 pyrrolidines have been found in the secretions of thief ants and fire ants of the genera Solenopsis and Monomorium. Among these, compounds 80-84 are simple pyrrolidines with two saturated linear all-carbon side chains only in Solenopsis latinode is there a secondary amine (82) and its methylated analog (85). One or two terminal unsaturations are present in compounds 86-91, which all possess a (hex-l-en)-6-yl chain and a 5-, 7-, or 9-carbon saturated chain. Compounds 93, 94, 96, 97, and 98 are the A-l-pyrrolines corresponding to pyrrolidines 80, 82, 90 (93 and 96 corresponding to 80, 94 to 82, and 97 and 98 to 90). 

Curiously, the synthesis of shihunine via a phenylcyclopropylimine (187) is the sole example of a simple pyrrolidine alkaloid obtained according to this general pyrroline synthesis (188) (Scheme 40). 

Fustero has devised an intramolecular version of the iminium ion catalysed conjugate addition of nitrogen in the preparation of a series of simple pyrrolidine and piperidine derivatives [115]. The reactions proceed in chloroform to give the target heterocycles in good yield and excellent levels of stereocontrol (Scheme 32). 

A simple pyrrolidine imide (10), derived from L-proline, brings about the direct formation of a -unsaturated ketones from unmodified ketones and aldehydes under mild conditions.31 Mechanistic investigation suggests a Mannich elimination process, rather than an aldol route. 

Simple Pyrrolidine Alkaloids.—It is well established that ornithine (1) is a key precursor in the biosynthesis of pyrrolidine alkaloids. Notably, the amino-acid (1) is utilized for the biosynthesis of nicotine (5) via the symmetrical intermediate putrescine (3), whereas the biosynthesis of tropane alkaloids, e.g. scopolamine (6), avoids any symmetrical intermediate1,2 (cf. Vol. 11. p. 1). 

While it is probably reasonable to draw general trends from this series, it should be kept in mind that most of the data came from different laboratories, as indeed there are four different reports for the simple pyrrolidine enamine that account for the range from 85 to 96%. Some of the factors that contribute to determining the regioisomeric composition of enamines are A -strain, which destabilizes the more substituted isomer, and A - -strain, which destabilizes the less substituted isomer (Scheme 6). The former effect was used by Johnson to effectively convert c/j-2,4-dimethylcyclohexanone to the trans isomer through formation of the less substituted pyrrolidine enamime, where a pseudo-axial orientation of the 2-methyl group reduces the level of A - -strain (equation... 

In addition to benzylisoquinolines, the family Lauraceae furnishes phenanthro-quinolizidine alkaloids such as the previously mentioned cryptopleurine (31) [77], a highly cytotoxic and vesicant substance first isolated from Cryptocarya pleurosperma [78]. These alkaloids are closely related structurally to the phenanthroindolizidines, a group of bases found in the families Asclepidaceae and Moraceae that are likewise vesicant. An example is tylocrebrine (56), which is elaborated by a Queensland plant from each family, Tylophora crebriflora [79] and Ficus septica [80], respectively. In the latter it occurs along with the seco analogue septicine (57), its presumed biosynthetic precursor. Apart from phenanthroindolizidines, certain Ficus spp. produce some simple pyrrolidine bases such as ficine (58) that are noteworthy because of their flavonoid substituents [81],... 

The decarboxylated diamino acids seem to play a special role in the synthesis of simple pyrrolidines and piperidines (386, 387). For example, pea diaminooxydase converts putrescine into A -pyrrolidine and cada-verine into dehydropiperidines. 

The Pyrrolidine Family. The alkaloid hygrine (3.7) isolated from leaves of plants from the Coca group is an example of a simple pyrrolidine derivative. It and other members of this family have been found to originate from the amino acid ornithine (Scheme 3.6). 

Simple pyrrolidines PI = Hygrine P2 = Cuscohygrine P3-A = Hygrolines P3-B = Norhygrine P3-C = Anahygrine P3-D = Ai-Methylpyrrolidinylhygrines ... 

Subfamily tribe/clade species Simple pyrrolidines Nicotinoids 3a-Acyloxytropanes (3ct-AOT) 3p- AOT References (Tropanes only For till species, especitdly those without reference, see (also) Lounasmtia and Tamminen 1993 and references therein)... 

Tribe clade species Simple pyrrolidines Nico- tinoids Simple tropanes 3a-Acyloxytropanes 3p- Acyloxytropanes References... 

The term simple pyrrolidines is chosen here for those alkaloids whose structure is characterized by one or two isolated pyrrolidine rings without any other heterocycUc moiety. This restriction separates them from the biogenetically closely related nicotinoids and tropanes, respectively. Shortly after the discovery of the famous tropane alkaloid cocaine (Niemann 1860) a second alkaloid, hygrine , was discovered in the leaves of Erythroxylum coca Lam., Erythroxylaceae (Wohler and... 

Oxopropyl)hygrine 5-(2-Hydroxypropyl)hygrine 5-(2-Hydroxypropyl)hygroline Fig. 3.3 Simple pyrrolidine alkalaids of the hygrine and hygroUne type... 

Quantitative information concerning simple pyrrolidine alkaloids is rather rare. The roots of Nicandra physalodes contained 0.1% hygrine whereas five Physalis spp. contained considerably less (Romeike 1965a,b). The content of the epigeal parts of N. physalodes was even extremely low. Surprisingly, cuscohygrine turned out to be the main alkaloid of Datura discolor roots with a concentration of 0.06% which amounts to 20% of the total alkaloid content (0.31%). This is in contrast with other Datura spp. where tropanes (hyoscyamine/scopolamine) represent the principal alkaloids (Evans and Somanabandhu 1974a). 

Chemotaxonomic Relevance. The existing data for an intrafamilial evaluation of this topic are full of gaps in case of the Solanaceae (Table 3.1). However, since simple pyrrolidines are plesiomorphic characters shared with the well-studied Convolvulaceae (Table 3.2) and at least the occurrence and distribution of cuscohygrine is also well-documented in the Solanaceae, it might be that there is a similar tendency in both Solanales families. 

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