Enediyne Compounds Equipped with Acid‐, Base‐ and Photo‐Sensitive Triggering Devices. Chemical Simulation of the Dynemicin A Reaction Cascade

Abstract

Fig. 3. Structure of the phenalenium ion o f 3 . CH,CI, (X = I) viewed perpendicular to the phenalenium plane with bond lengts [pm] and angles [' I (in brackets, standard deviations in units of the last decimal given) 1111.cation was found for the phenalenium moiety, and individual polymethine units could not be identified. Remarkable, however, is the high bond order, which can be deduced from the short C(2)-C(3), C(S)-C(6), and C(8)-C(9) distances (Fig. 3).113 (X = Br), which has the same structure as the iodide with respect to the phenalenium ion, exhibits a particularly interesting lattice packing: the cations of 3 are stacked with an ecliptical arrangement of the phenalene skeletal frameworks along the c-axis, whereby the dimethylamino groups of neighboring cations are in exactly staggered positions. The interplanar distances alternate between 376 and 396 pm;Fig. 4. Structure of 3 (X = Br): view of a pair of phenalenium ions along the stacking axis (c-axis) [12].the shorter distance is apparently linked to the hexagonal network of bromide ions, which surround the pair of phenalenium ions with the shorter interplanar distance (Fig. 4).[lZ1 The recent isolation of the novel anticancer agent dynemicin A (1)l1] and the proposed cascade of reactions Engineering Research Council (SERC) for the award of a NATO fellowship. 1032 0 VCH Verlagsgesellrschaft mbH. W-6940 Weinheim. 1991 0570-0833~9ll0808-1032 $3.50+.25/0 Angew. Chem. 1n1. Ed. Engl. 30 (1991) No. 8 ( M e + H): 561.1162, found 561.1162.-24: R, = 0.63 (silica, 50% diethyl ether in benzene); 'H NMR (300 MHz, [D8]THF:D,0, 1O:l): b = 8.53 (d, J = 8.8 Hz, 1 H, aromatic), 7.45-7.10 (m, 5H, aromatic), 6.88 (d, J = 2.5 Hz, 1 H, aromatic), 6.63 (dd, J = 8.8, 2.5 Hz, 1 H, aromatic), 5.97 (d, J = 10.0 Hz, 1 H, olefinic), 5.78 (dd, J = 10.0, 1.6 Hz, 1 H. olefinic), 5.46 (br.s, l H , CHN), 2.35-1.55 (m, 6H, CH,). -30: R,=0.33 ( 5 % methanol in methylene chloride); 'HNMR (300 MHz, CDCI,): 6 =7.43 (dd, J = 5.3, 3.5 Hz, 1 H, aromatic), 7.25-7.10 (m, 4 H , aromatic), 6.56 (dd, J = 8.4, 2.2 Hz, 1 H, aromatic), 6.53 (d, J = 2.2 Hz, 1 H, aromatic), 5.58(s,lH,CHN),5.46(t,J=5.6Hz,lH,CH,NHCON),3.19-2.95(m, 2 H. CHZNHCON), 2.80 (dt, J = 11.3, 6.

Design and Synthesis of Heterocycle‐Fused Enediyne Prodrugs Activable at Will

“…A similar route was followed also to prepare a second lactenediyne bearing at the β-lactam nitrogen a silyl removable group, in order to render such nitrogen atom able to be further elaborated. The overall yield of this synthesis, although longer than the previous one, was good, and it allowed us to prepare the final enediyne (27), as well as its silylated analogue, in a gram scale. Also in the case of lactenediynes with two additional handles a similar approach for the synthesis of the cyclic enediyne system was followed, 18 however this time the β-lactam (29) was assembled more convergently, by the use of a Staudinger condensation with (28), having a styryl ISSN 1424-6376…”

“…The final cyclization was carried on with the Nozaki reaction, so we converted in two high yielding steps the silyl enediyne into iodo enediyne (26). After oxidation of the alcohol, treatment with chromous chloride gave the desired products (27) in very good yields (Scheme 5). A similar route was followed also to prepare a second lactenediyne bearing at the β-lactam nitrogen a silyl removable group, in order to render such nitrogen atom able to be further elaborated.…”

8-Methoxy-2-methylquinoline

“…The title compound was synthesized by literature methods (Leir, 1977;Kitamura et al, 2000). Quinoline derivatives have been shown to have anti-cancer and anti-malarial properties (Lee et al, 1991;Nicolaou et al, 1991). For bond-length data, see: Allen et al (1987).…”

“…Complexes containing the quinoline moiety can have pharmacological activity. Quinoline derivatives with additional substituents have good in anti-cancer and anti-malarial properties (Lee et al, 1991;Nicolaou et al, 1991) and this has aroused our inerest. Herein we describe the synthesis of the title compound and have determined its crystal structure.…”

A convergence of photo‐bergman cyclization and intramolecular chain collapse towards polymeric nanoparticles

“…Photo‐induced Bergman cyclization was uncovered in the 1990s by Sugiura,42 Nicolaou,43 and Wender 44. Later, Turro and Nicolaou revealed that simple artificial enediynes could also undergo cycloaromatization upon photo‐irradiation 45.…”