Intramolecular isomünchnone cycloaddition approach to the antitumor agent camptothecin

Total Synthesis of Camptothecin and SN-38

“…K 2 CO 3 (2.76 g, 0.02 mol) was added to a solution of compound 17 (3.59 g, 0.01 mol) and compound 5 (2.09 g, 0.01 mol) in DMF (50 mL) under nitrogen. Then the mixture was heated for 4 h at 50 °C, and poured into 200 mL of 1 N HCl solution, extracted with dichloromethane, dried with anhydrous Na 2 SO 4 , and evaporated to dryness to afford crude 18, which was further purified by trituration with petroleum ether/ethyl acetate (15 mL) to give pure 18 as an offwhite solid (4.38 g, 90% yield): 1 H NMR (500 MHz, CDCl 3 ) δ 0.95 (t, J = 6.5 Hz, 3H), 1.17 (S)-4,11-Diethyl-4-hydroxy-9-methoxy-1H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione (19). A mixture of bromoquinoline 18 (4.87 g, 0.01 mol), palladium(II) acetate (0.22 g, 1.0 mmol), anhydrous K 2 CO 3 powder (3.46 g, 0.025 mol), and triphenylphosphine (1.05 g, 4.0 mmol) in 150 mL of toluene was brought to reflux under nitrogen.…”

Total Synthesis of Camptothecins: An Update

“…23 An isomünchnone [3+2] cycloaddition strategy was recently used by Kanazawa and co-workers to assemble the D ring of CPT (Scheme 10). 24 Olefin 73 was first acylated with oxalyl chloride, and the resulting acid chloride was treated with diethylamine to provide the desired α-ketoamide 74 as a 10:1 mixture of E/Z isomers. The nucleophilic addition of ethylmagnesium bromide to 74, followed by the desilylation of the resulting alcohol and the oxidation of the sulfide with m-chloroperbenzoic acid afforded the E-hydroxy sulfone 75.…”

Synthesis of Fused Quinoline Derivatives from Easily Accessible N‐(2‐aminobenzylidene)‐4‐methylanilines under Catalyst‐Free Conditions in Water

“…One of the simplest, readily available and highly stable equivalents of 2‐aminoarylaldehydes are N ‐(2‐aminobenzylidene)‐4‐methylanilines, [18] which can be obtained from highly stable 2‐nitrobenzaldehyde in two steps. N ‐(2‐Aminobenzylidene)‐4‐methylanilines were previously employed as precursors to access nitrogen heterocycles in the presence of PPTS, [18a] p ‐TSA, [18b–d] piperidine [18e] or cerium(IV) ammonium nitrate (CAN) [18f] in toluene or ethanol under reflux conditions.…”