Synthesis of pyrano[4,3-b]indoles as conformationally restricted analogs of the serotonin antagonist ICS 205-930 and as precursors to 2-vinylindoles

Macor, John E.; Ryan, Kevin; Newman, Morris

doi:10.1021/jo00281a018

Cited by 23 publications

(5 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The generality of our approach is demonstrated by performing the arylation of other related 5-membered heterocycles such as the 2-methylindole derivative 14 and the 2-methylbenzimidazole 15 . In these cases, TMPZnCl·LiCl ( 1 ) proved to be a suitable base, and a complete zincation could be obtained within 1 h at 25 °C.…”

mentioning

confidence: 99%

Benzylic Arylation of 2-Methyl-5-membered Heterocycles Using TMP-Bases

2012

View full text Add to dashboard Cite

show abstract

mentioning

confidence: 99%

Benzylic Arylation of 2-Methyl-5-membered Heterocycles Using TMP-Bases

2012

View full text Add to dashboard Cite

show abstract

“…THF was used as purchased from Wako Chemical. Ethyl [10]; 0.769 g, 2.15 mmol), NBS (¼ N-bromosuccinimide; 0.384 g, 2.156 mmol), and benzoyl peroxide (0.011 g, 0.03 mmol) in CCl 4 (30 ml) was heated at reflux for 6 h, and the solvent was evaporated. Washing the residue with hexane gave 6 (0.877 g, 93%).…”

Section: Experimental Partmentioning

confidence: 99%

“…First, we focused on the preparation of 9-substituted aziridinomitosene, in which a appropriate substituent could be converted to the carbamoyloxymethyl moiety present in mitomycins. However, attempts for the aziridination between ethyl 2-formyl-1-[(4methylphenyl)sulfonyl]-1H-indole-3-carboxylate (7), which was prepared from ethyl 2-methyl-1-[(4-methylphenyl)sulfonyl]-1H-indole-3-carboxylate (5) [10] in two steps as shown in Scheme 2, and a guanidinium salt 8 under standard reaction conditions, using either tetramethylguanidine (TMG) in THF or NaH in DMF, unfortunately failed.…”

mentioning

confidence: 99%

Synthesis of the Aziridinomitosene Skeleton by Application of Guanidinium Ylide‐Mediated Aziridination

Kojima

Takahata

David

et al. 2013

Helvetica Chimica Acta

View full text Add to dashboard Cite

An aziridinomitosene skeleton, a basic core of mitomycin antibiotics, was straightforwardly prepared from N-(p-toluenesulfonyl)indole-2-carboxaldehyde in 16% overall yield by successive reactions of guanidinium ylide-mediated aziridination, InCl 3 -catalyzed epimerization of trans-3-(indol-2-yl)aziridine-2-carboxylate, leading to the cis-derivative, and dehydrative cyclization.Introduction. -Mitomycins are antibiotics isolated from Streptomyces species [1], and mitomycin C, among them, has clinically been used as an anticancer drug [2]. Aziridinopyrroloindole, composed of a 6-5-5-3 ring system, is the core skeleton of mitomycin antibiotics and is generally called as either aziridinomitosane or aziridinomitosene depending upon the saturation of the indole unit. Many groups have attempted at the synthesis of mitomycin antibiotics due to their interesting biological activities, and Kishi and co-workers [3], and Fukuyama and Yang [4] have skillfully achieved total syntheses of natural mitomycins. Although various synthetic approaches to aziridinomitosane [5] and aziridinomitosene [6] skeletons have also been examined, the use of bond connection between C(3) and N(4) (cf. the atom numbering of aziridinomitosene in Scheme 1) in the final construction of the ring system has never been reported to the best of our knowledge. We have established a unique guanidinium ylide-mediated aziridination reaction of an aromatic [7] [8] or unsaturated [9] aldehyde, in which trans-3-(indol-2-yl)aziridine-2-carboxylate (trans-2; Scheme 1) could be obtained, when indole-2-carboxaldehyde (1; Scheme 1) is used as an aldehyde source. Herein, we describe a straightforward construction of a model aziridinomitosene skeleton from 3-(indol-2-yl)aziridine-2-carboxylate.Results and Discussion. -Our synthetic strategy toward the aziridinomitosene skeleton 3 or 4 is outlined in Scheme 1, in which three reactions are combined: i) Scheme 2. Trials for Aziridination of Ethyl 2-Formyl-1H-indole-3-carboxylate 7 Scheme 3. Aziridination of (Silyloxy)methyl-Substituted 1H-Indole-2-aldehydes and Trials for Epimerization of the trans-Aziridines Formed

show abstract

“…On the other hand, the regioselective alkylation of the ketone (1) is an alternative way to obtain the same derivative (6). On one hand, the preparation of the tetracyclic compound (6) could be achieved from already methyl substituted precursors.…”

Section: Cyclohept[b]indol-12-one Derivatives (A)mentioning

confidence: 99%

“…Found: C, 78.02; H, 6.68: N, 4.90.5,6-Dimethyl-5,6,7,12-tetrahydrobenzo[4,5]cyclohepta[b]indol-l2-one(6).Method A: To a solution of 5 (500 mg, 1.70 mmol) in 1.2-dichloroethane (15 mL) was added trifluoroacetic anhydride (0.60 mL, 4.26 mmol), and the mixture was stirred at rt for I h, then boron trifluoride etherate (0.21 mL, 1.70 mmol) was added. ): 6 1.56 (d, 3H, J = 7.2 Hz, CH4, 3.1 1 (dd, IH, J = 7.7, 13.2 Hz, CH2), 3.35-3.52 (m, IH, CH?…”

mentioning

confidence: 99%