Total Synthesis of (±)‐Strictamine

Abstract

The total synthesis of strictamine has been achieved in nine steps from a known enol triflate. Characteristic features of our approach included: a) creation of a C7 all-carbon quaternary stereocenter at an early synthetic stage; b) use of an N,N-dimethyl tertiary amine as a surrogate of the primary amine for the rapid build-up of a functionalized 2-azabicyclo[3,3,1]nonan-9-one skeleton (achieved by using a reaction sequence of α-bromination of the ketone, followed by a stereoconvergent intramolecular nucleophilic substitution reaction); and c) a late-stage construction of the indolenine unit.

Asymmetric Total Syntheses of the Akuammiline Alkaloids (−)‐Strictamine and (−)‐Rhazinoline

“…Strictamine and associated congeners ( 1 – 3 , Scheme A) belong to a subfamily of the akuammiline alkaloids that contain a unique methanoquinolizidine structural unit and diverse substituents with differentiated stereochemistry at C16, having challenged synthetic chemists for decades . In 2016, Zhu's group reported a successful synthetic approach to (±)‐strictamine using a sequence of ring forming reactions; however, the final Ni‐mediated E‐ring formation suffered from low efficiency . Later, a few groups including Fujii/Ohno, Gaich,, and Snyder, as well as our group independently reported formal syntheses of strictamine by intercepting Zhu's intermediate.…”

Formal Total Synthesis of (±)‐Strictamine by [2,3]‐Sigmatropic Stevens Rearrangements

“…Over the past decades, akuammilinea lkaloids have interested the synthetic community owing to their unique chemical structure and biological activity. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] In particular,s trictamine (1)w as first synthesized in 2015 and 2016 by the groups of Garg (enantioselective), [18] Zhu (racemic), [19] Ohno (formal), [20] and ours (formal). [21] Biosynthetically,s trictamine (1)b elongs to the group of monoterpenoid indole alkaloids, which are derived from (E)-geissoschizine (4).…”

Formal Total Synthesis of (±)-Strictamine

“…The residue was purified by silica gel flash column chromatography (AcOEt/n-hexane = 1/9) to afford 19 (88.7 mg, quant.) as a white amorphous solid; IR (ATR) νmax cm −1 : 3020, 2958, 2933, 2877, 1726, 1684, 1528, 1396, 1366, 1356, 1259, 1215, 1159, 1100, 1066, 10181 H NMR (CDCl3, 400 MHz, at 55 °C) δ ppm: 7.93 (1H, d, J = 8.2 Hz), 7.55 (1H, ddd, J = 7.8, 7.8, 1.4 Hz), 7.43 (1H, ddd, J = 7.8, 7.8, 1.4 Hz), 7.40 (1H, d, J = 8.2 Hz), 4.89 (1H, dd, J = 8.5, 8.5 Hz), 4.34 (1H, br-s), 3.87 (1H, ddd, J = 13.7, 9.1, 6.4 Hz), 3.66 (1H, br-s), 3.32 (1H, br-s), 2.37-1.86 (5H, m), 1.47 (9H,s),0.76 (9H,t,J = 7.7 Hz),0.35 (3H,dq,J = 15.4,7.7 Hz),0.27 (3H,dq,J = 15.4,7.7 Hz);13 C NMR (CDCl3,100 MHz,at 55 °C) δ ppm: 204.8,154.5,150.1,134.7,132.1,130.6,128.1,125.6,80.5,75.5,59.4,58.6,41.0,32.4,31.5,28.4,25.7,6.6,4.8 was added Dess-Martin periodinane …”

“…8.22 (1H, dd, J = 8.2, 1.4 Hz), 7.71 (1H,ddd,J = 7.8,7.8,1.4 Hz),7.54 (1H,ddd,J = 7.8,7.8,1.4 Hz),7.46 (1H,d,J = 8.2 Hz),4.80 (1H,4.28 (1H,J = 7.3 Hz),3.50 (1H,ddd,J = 13.7,13.7,4.4 Hz),3.07 (1H,dd,J = 19.9,9.4 Hz),2.76 (1H,dd,J = 19.9,10.1 Hz),2.71 (1H,d,J = 10.1 Hz),2.49 (1H,ddd,J = 13.7,6.5,6.5 Hz),m),1.47 (9H,s); 13 C NMR (CDCl3,150 MHz,at 55 °C) δ ppm: 206.0,200.9,154.1,147.5,134.1,131.8,129.2,129.1,126.1,81.4,68.5,58.5,40.3,37.4,35.9,28.4,…”