Synthese von trans‐7‐Methyl‐2,16‐dioxo‐eicosen‐(14)

Abstract

The synthesis of trans‐7‐methyl‐2,16‐dioxoeicosen‐(14) dicarbonyl‐compounds is described.

Enantioselective total syntheses of pumiliotoxin B and pumiliotoxin 251D. A general entry to the pumiliotoxin A alkaloids via stereospecific iminium ion-vinylsilane cyclizations

“…161.0 (s, 0=0), 149.3 (d,C=CH), 134.6 (s, C=CH), 81.2 (s, C-l) 70.5 (d, CHN), 46.2 (t, NCH2), 43.8 (t, CH2CO), 32.9 (t, C=CCH2CH2), 26.6 (t, CH2CH2N), 26.4 (q, OCMe), 25.8 (t, CH2CHN), 23.2 (CH2Me), 14.6 (CH2Me), 1.10 (q, Me3Si); MS (isobutane, Cl), m/z 310 (MH), 186, 156, 139, 114. (S)-l-Heptyn-3-ol (25). Using the general procedure developed by Pirkle,291 racemic l-heptyn-3-ol (30.0 g, 0.268 mol) was converted to the chloroformate ester and reacted with (/?…”

“…Carbamate 26 (6.3 g, 20 mmol) was cleaved to the alcohol with CljSiH (3.4 g, 25 mmol) as described by Pirkle.291 Bulb-to-bulb distillation gave 1.53 g (68% from 26) of (S)-l-heptyn-3-ol (25): 99% pure by GLC analysis,511 [a]25D -18.8 (c 5.2, dioxane).27 250-MHz 'H NMR analysis of the (H)-MTPA ester28 of 25 indicated an enantiomeric purity of >98%.…”

“…A 1.86-g (10.1 mmol) sample of this alcohol was converted to the methyl carbonate derivative exactly as described by Macdonald30 to give 2.13 g (87%) of the pure silyl carbonate 27: 98% pure by GLC analysis;511 [a]25D -69.9 (c 3.35, CHClj); IR (film) 2175, 1705, 1260 cm"1; NMR (250 MHz, CDClj) 5.23 (t, J = 6.4 Hz, OCH), 3.80 (s, Me), 1.6-1.8 (m), 1.3-1.5 (m), 0.91 (apparent t, J = 7.1 Hz, CH2Mí•), 0.17 (s, MejSi); l3C NMR (23 MHz, C6D6) 6 155.7, 103.6, 91.2, 68.8, 54.9, 35.4, 27.8, 22.9, 14.0, 0.25; MS (isobutane Cl), m/z 242 (MH), 167, 149, 93, 89, 73. Preparation of 27 from enantiomerically pure alcohol 25 provided 27: [<x]25D -87.6 (c 5.3, CHClj). Reaction of 27 (100 mg, 0.413 mmol, [a]25D -69.9) with the copper reagent prepared in THF (3 mL) from Cul (52.2 g, 0.826 mmol) and MeMgBr (0.53 mL of a 3.1 M solution in ether) was accomplished using the procedure detailed by Macdonald.30 TLC analysis showed that the reaction was complete after 1 h at 0 °C.…”

“…A mixture of a portion of this sample of 30 (58.5 mg, 0.188 mmol), paraformaldehyde (11.3 mg, 0.376 mmol), and absolute EtOH (0.6 mL) was sealed in a 5-mL ampule and heated at 80 °C for 2-4 h. After cooling to 23 °C unreacted paraformaldehyde was removed by filtration, and the filtrate was concentrated to give the crude oxazolidine 31: NMR (250 MHz, CDC13) 5.78 (d, 7=10 Hz, C=CH), 4.43 (AB q, 7 = 6. 25 Hz, = 14.9 Hz, NCHHO), 3.3-3.4 (m, NCH), NCTTH),NCH.H),2.34 (d,7= 13.6 Hz, Cf/HC=C), 2.09 (d, 7 = 13.6 Hz, CHHC=C), 2.2-2A (m), 1.7-2.0 (m), 1.2-1.4 (m), 1.10 (s, Me), 0.94 (d, 7 = 6.2 Hz, CH Me), 0.88 (t, 7 = 6.5 Hz, CH 2Me), 0.15 (s, Me3Si); MS (isobutane Cl), m/z 324 (MH), 126, 125, 114, 84, 83, 73, 70. A solution of this oxazolidine sample, camphorsulfonic acid (21.8 mg, 0.087 mmol), and absolute EtOH (0.6 mL) was sealed in a glass ampule and heated at 80 °C for 1 day. The reaction was then concentrated, the residue was partitioned between CH2C12 (20 mL) and NaHC03 (5 mL, saturated aqueous), and the organic layer was dried (Na2S04).…”

Enantiospecific total synthesis of dendrobatid toxin 251D. A short chiral entry to the cardiac-active pumiliotoxin A alkaloids via stereospecific iminium ion-vinylsilane cyclizations

“…With the general viability of the approach established, our attention turned to the preparation of the chiral 25ID sidechain, which was conveniently secured as follows (eq 2). Reduction of l-heptyn-3-one (15)15 with fl-3-pinanyl-9-borabicyclo[3.3.1 ] nonane (7) All compounds reported were homogeneous by TLC and showed NMR, 13C NMR, IR, and mass spectra consistent with the assigned structure; the molecular composition of all key intermediates was determined by highresolution mass spectrometry or combustion analysis. Partial characterization data for selected intermediates are as follows.…”