Quinolines pentacyclic

Bennasar et al. reported a new radical-based route for the synthesis of calothrixin B (378) (869). This synthesis starts from the 2,3-disubstituted N-Boc indole 1558 and uses a regioselective intramolecular acylation of a quinoline ring as the key step for the construction of the calothrixin pentacyclic framework. Chemoselective reaction of in s/fM-generated 3-lithio-2-bromoquinoline [from 2-bromoquinoline 1559 with LDA] with the 3-formylindole 1558 followed by triethylsilane reduction of the... 

The pentacyclic quinoline alkaloid camptothecin (1) contains in addition to the quinoline system (rings A and B) a pyndone unit (ring D) and a lactone ring (E) Compound 1 also includes one stereogenic center (at C-20), which has the -configuration... 

Irinotecan (1) is a derivative of the pentacyclic quinoline alkaloid camptothecin (2) the latter was first isolated from the heartwood of the tree species Camptotheca acuminata (Nyssacea) by Wall et al. in 1966.1 Two years later A. T. McPhail and G. A. Sim determined the structure of 2 by X-ray analysis.2... 

Quinoline, on treatment with zinc and acetic anhydride in THF, readily gives the pentacyclic quinobenzazepine skeleton (52) (Scheme 36) <95SL603>. 

The pentacyclic dimers (27) and (28) are obtained from quinoline by treatment with a Zn/Ac20/THF reagent <95SL603> and bromination of the azabicyclo[7.3.1]enediyne (29) affords the pyrroloazepine (30) <95TL4539>. 

Formation of pentacycle 55 was consistent with the radical addition-quinoline rearomatization-overoxidation sequence depicted below. Thus, the initially formed acyl radical L undergoes regioselective cyclization upon the 4-position of the quinoline ring to give the azacyclohexadienyl radical M, which is probably oxidized by hydrogen abstraction at the hands of the initiator AIBN <04AGE95>. A new hydrogen abstraction at the doubly... 

The reductive cyclization protocol was then applied to a suitably A-protected radical precursor to allow further access to the alkaloid calothrixin B. Satisfactorily, 2-indolylacyl radicals derived from A-(methoxymethyl) selenoester 57 underwent cyclization under TTMSS-AIBN conditions with an even higher efficiency than their A-methyl counterparts. The reaction nevertheless followed a different course as, after the radical addition and quinoline rearomatization, pentacyclic phenol 58, a fully aromatic tautomeric form of ketone P, was isolated in 90% yield. The same phenol 58 was isolated although in lower yields (50-70%) using either stannane-AIBN or AIBN-irradiation protocols. 

Camptothecin (CRT, 6, Figure 2.2) was first isolated from the Chinese ornamental tree Camptotheca acuminata Decne, also known as the tree of joy and tree oflove. It occurs in different plant parts such as the roots, twigs, and leaves. It is a member of the quinoline alkaloid group and consists of a pentacyclic ring structure that includes a pyrrole quinoline moiety and one asymmetric center within the a-hydroxy lactone... 

On treatment with zinc in acetic anhydride, quinoline is readily transformed to the product 46 showing a pentacyclic quinobenzazepine skeleton. This formal reductive dimerization process is likely to be initiated by SET (single electron transfer) of the A-acetylchinolinium intermediate 45 followed by radical dimerization via 4-position [94]. 

This strategy led to the synthesis of a small compound Hbrary of indoloiso-quinolines with functional group variations on the aromatic rings and with yields between 42 and 95%. Furthermore, a concise synthesis of the NPs themselves was achieved by employing this domino reaction sequence as a key transformation. Pentacyclic substrate 9 was obtained through the silver-catalyzed domino polycy-clization between acetylenic indole-2-carbaldehyde 7 and anihne 8. Pentacycle 9 was subsequently transformed into homofascaplysin C (10) in only one formylation step (overall yield of 54%), while two further transformations provided fascaplysin (11) in overall yield of 52% (Scheme 13.2). 

Hdpfner and co-workers used this cyclization to form a unique pentacyclic carbazole that can form hydrogen bonds for complementary binding vital for supramolecular process. Starting with a-tetralone and quinolin-8-amine the initial cyclization provided pyrido[3,2-g]indole 21, in which some oxidation of the ethano bridge occurred to provide the desired product 22. Completion of the oxidation occurred with excess DDQ to provide the desired carbazole. 

An intramolecular 1,3-dipolar cyloaddition protocol involving as key step in situ desilylation of azido alkyne 176, coupled with microwave irradiation, successfully furnished triazolobenzoxazepine 177 (13TL6005). A tandem 1,3-dipolar cycloaddition/N—O single bond insertion process between quinoline N-oxides and aryne precursors afforded pentacyclic oxazepino[4,5-(j]quinolines 178 with, in most cases, concomitant formation of the corresponding 2-(2-hydroxyphenyl)quinolines (13BCJ615). 

Other minor quinoline alkaloids are those of quinicine (quinotoxine) class (5-6) [58, 59, 64, 67, 71, 72]. Besides quinoline alkaloids produced by Cinchona species, there are also a number of indole-t3q)e minor alkaloids classified as cinchonamines (7-9) [67, 72-76] or dimeric cinchophyllamine type (alternative name cinchophylline) (10) [76-81]. Other stractures include quinamines (11) [61-63, 73, 76, 79, 82, 83], tetracyclic 3-isocorynantheol (12) [54, 84], or less typical for Cinchona species (C. ledgeriana and C. pelleteriana) pentacyclic aricine (13) [54, 79, 85, 86]. Their stractures are given in Fig. 21.3. 

In 2006, an MCR pathway to pentacyclic quinoline derivatives 439 was established by Bhuyan et al. (Scheme 13.91) [182], Novel annelated quinolines have been prepared in a three-component reaction under solvent-free conditions at high temperatures. In addition to Meldrum s acid 112 and pyrrolidine 438, a variety of other CH acids and amines have successfully been applied in this reaction. 

On treatment with zinc in acetic anhydride, quinoline is readily transformed to the polycyclic product 56 showing a pentacyclic quinobenzazepine skeleton. This formal... 

Li has described the preparation of complex pentacyclic systems containing an indeno[2,l-c]quinoline core (compounds 125) by treatment of o-phthalaldehyde with 4-hydroxy-6-methyl-2/f-pyran-2-one and cyclic enaminones [85]. The domino process summarized in Scheme 3.37 was proposed to explain this transformation. 

Scheme 337 Multicomponent, diastereoselective route developed by Li for the synthesis of pentacyclic compounds derived from the indeno[2,l-c]quinoline system.

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