The Crystal Structure of 1,2‐Didehydrocrotalanine Picrate: A Macrocyclic Pyrrolizidine Alkaloid Analogue

Abstract

Summary1,2-Didehydrocrotalanine (2) is the first synthetic macrocyclic pyrrolizidine alkaloid analogue to be studied by X-ray crystallography. The crystal structure was solved by multisolution direct methods and refined by full-matrix least-squares to R = 0.036 for 693 reflections. The alkaloid analogue has an 1 1-membered macrocycle containing two ester groups with their carbonyl groups nearly antiparallel.Introduction. -The present analysis continues our structural studies of pyrrolizidine alkaloids whose structure and/or toxicity is of particular interest [ 1-51. Pyrrolizidine alkaloids frequently occur naturally as macrocyclic diesters in which a pyrrolizidine diol (necine) is esterified with a diacid to produce 11-, 12-, 13-or 14-membered rings [6] [7]. Retronecine (1) is the most common necine and its macrocyclic diesters are hepatotoxic [8]. About 25 naturally occuring 1 1-membered pyrrolizidine alkaloids have been isolated, but synthesis of these macrocyclic diesters has proved difficult [9]. Recently, Robins and co-workers [ 101 have synthesised one natural and six unnatural 1 1-membered macrocyclic diesters from (+ )-

Grantianine, C18H23NO7: a pyrrolizidine alkaloid

“…Atom C(9) lies 0.19 (1)/~ from the unsaturated-ring plane [planar to within 0.01 (1) A]. A similar situation has been observed in 1,2-didehydrocrotalanine (Stoeckli-Evans & Robins, 1983) and in PA's with a 12-membered macrocycle where deviations of as much as 0.25 (1)A have been observed (Mackay & Culvenor, 1982).…”

“…The ring fusion distance N(4)-C(8) is 1.490 (7)A, close to the average value (1.50/~,) observed previously for the free alkaloids. In two PA's studied as quarternary salts values of ea 1.54 A have been observed (Stoeckli-Evans & Robins, 1983;Sawhney, SenGupta, Hossain & van der Helm, 1983). Atom C(9) lies 0.19 (1)/~ from the unsaturated-ring plane [planar to within 0.01 (1) A].…”

“…The synthetic analogue 1,2-didehydrocrotalanine (Stoeckli-Evans & Robins, 1983), and trichodesmine (Tashkhodzhaev, Telezhenetskaya & Yunusov, 1979) have the ester carbonyl bonds antiparallel. In grantaline (Mackay & Culvenor, 1983), which has an oxetane ring fused to the macrocycle at bond C(13)-C(14), the carbonyl bonds lie on the same side of the macrocycle but are directed outwards from it with an angle of 94 ° between the bonds.…”

Structure of a ten-membered macrocyclic diester of (+)-retronecine, C12H15NO4: a pyrrolizidine alkaloid analogue

“…The X-ray structure of the ten-membered macrocycle shows that the carbonyls of the ester groups are nearly antiparallel on opposite sides of the ring system. This conformation of the ester groups is found in only three 1 l-membered macrocycles containing retronecine [grantianine (Stoeckli-Evans & Robins, 1984), 1,2-didehydrocrotalanine (Stoeckli-Evans & Robins, 1983)and trichodesmine (Tashkhodzhaev, Yagudaev & Yunusov, 1979)] and all 12-membered macrocyclic PA's containing retronecine studied so far Cano & Garcia-Blanco, 1978) and retrorsine (Stoeckli-Evans, 1979)]. The dihedral angle between the ester groups defined by the planes C(9), O(10), C(11), O(11) and O(14), C(14), O(15), C (7) is 159 (5) °.…”

ChemInform Abstract: Conformation of an Eleven‐Membered Lactone: Structure of (E,13R,14S)‐ 13‐Hydroxy‐17‐nor‐8,9‐secolabd‐9(11)‐en‐8,14‐olide.

“…The eleven-membered dilactone rings in the pyrrolizidine alkaloids can therefore be regarded as analogues of cycloundeca-1,6-diene with both C--~C bonds replaced by CO--OR bonds. Nevertheless, the conformations of the dilactone rings of the alkaloids in the solid state (Sussman & Wodak, 1973;Stoeckli-Evans, 1979Stoeckli-Evans & Robins, 1983;Mackay, Sadek & Culvenor, 1984;Brown, Burton, Robins & Sim, 1986;Robins & Sim, 1987) do not correspond to the conformations of cycloundeca-l,6-diene derived by force-field calculations.…”