11.1, 1.6 Hz, 1H), 3.94 (dd, J = 10.3, 6.4 Hz, 1H), 3.26 (s, 3H), 3.18 (dd, J = 11.0, 2.2 Hz, 1H), 3.01 (d, J = 7.9 Hz, 1H), 2.77 (s, 3H), 2.45 (bdd, J = 10.2, 7.9 Hz, 1H); 13C NMR (75 MHz, CDCl3): 161.6, 155.2, 149.8, 138.0, 136.9, 136.7, 128.0, 127.4, 127.3, 127.2, 126.8, 126.7, 126.5, 126.3, 126.2, 90.0, 80.4, 76.4, 75.8, 71.3, 71.2, 70.6, 68.3, 38.8, 27.6, 27.0, 26.8; HRMS: 554.2420 (calculated for C33H34N2O6: 554.2417).
(1S,2R,3R,3aS,9bS)-1,2,3-Tris-benzyloxy-6,8-dimethyl-2,3,3a,4,6,9b-hexahydro-1H-5-oxa- 6,8-diaza-cyclopenta[a]naphthalene-7,9-dione (11). Oil; Rf: 0.33 (50% ethyl acetate in hexanes); [a]D: -2.0 (c 1, CHCl3); IR (neat): 3075, 3030, 2930, 2900, 1700, 1640 cm-1; 1H NMR (600 MHz, C6D6): 7.43 (d, J = 7.4 Hz, 2H), 7.28-7.03 (m, 13H), 4.81 (d, J = 12.2 Hz, 1H), 4.68 (d, J = 12.2 Hz, 1H), 4.38 (d, J = 11.8 Hz, 1H), 4.35 (bs, 1H), 4.32 (d, J = 11.4 Hz, 1H), 4.30 (d, J = 11.9 Hz, 1H), 4.21 (d, J = 11.4 Hz, 1H), 3.96 (bs, 1H), 3.61 (bt, J = 3.9 Hz, 1H), 3.50 (bs, 1H), 3.43 (bs, 1H), 3.34 (s, 3H), 2.89 (s, 3H), 2.37 (dt, J = 13.6, 1.8 Hz, 1H), 1.20 (bd, J = 13.6 Hz, 1H); 13C NMR (75 MHz, CDCl3): 161.2, 155.4, 149.8, 137.6, 137.3, 136.7, 127.5, 127.4, 127.3, 127.0, 126.9, 126.7, 126.5, 126.4, 126.1, 86.3, 83.5, 76.2, 75.6, 71.3, 70.9, 70.4, 70.3, 35.4, 27.3, 27.0, 25.1; HRMS: 554.2415 (calculated for C33H34N2O6: 554.2417).
(1R,9S,10R,11R,12S)-10,11,12-Tris-benzyloxy-4,6-dimethyl-8-oxa-4,6-diaza-tricyclo[7.3.1.02,7] tridec-2(7)-ene-3,5-dione (12). Oil; Rf: 0.11 (50% ethyl acetate in hexanes); [a]D: -3.8 (c 1, CHCl3); IR (neat): 3050, 3020, 2920, 2850, 1690, 1620 cm-1; 1H NMR (300MHz, CDCl3): 7.45 (dd, J = 7.3, 2.0 Hz, 2H), 7.35-7.25 (m, 13H), 5.13 (d, J = 11.4 Hz, 1H), 4.84 (d, J = 10.5 Hz, 1H), 4.76 (bs, 2H), 4.72 (d, J = 10.5 Hz, 1H), 4.61 (d, J = 11.4 Hz, 1H), 3.67-3.62 (m, 2H), 3.59- 3.50 (m, 2H), 3.40 (s, 3H), 3.38-3.35 (m, 1H), 3.37 (s, 3H), 1.90 (dt, J = 14.1, 3.8 Hz, 1H), 1.68 (bd, J = 14.2 Hz, 1H); 13C NMR (75 MHz, CDCl3): 162.5, 156.0, 151.1, 138.8, 138.5, 138.1, 128.53, 128.50, 128.3, 128.0, 127.9, 127.7, 127.5, 87.5, 83.8, 83.5, 81.9, 76.3, 75.6, 72.6, 71.6, 28.8, 28.2, 25.9, 23.7; HRMS: 554.2421 (calculated for C33H34N2O6: 554.2417).
DKHDA reaction of (2S,3S,4S)-2,7-bis-benzyloxy-3,4-isopropylidenedihydroxy-hept-5-enal (14) with N,N-dimethylbarbituric acid (4). Aldehyde 14 was prepared from alcohol 13 (400 mg, 1 mmol) according to the literature.14e After aqueous workup the solvent was removed under reduced pressure and the residue was dried thoroughly under high vacuum for several hours. Then, acetonitrile (10 ml) was added followed by 4 (170 mg, 1.1 mmol), EDDA (10 mg) and anhydrous Na2SO4 (500 mg). The mixture was heated to reflux until TLC indicated the consumption of starting material (about 4 hours). The solvent was removed under reduced pressure and the mixture was purified by column chromatography using 25% ethyl acetate in hexanes as eluent to afford product 16 (230 mg, 43% overall from 13, as an inseparable mixture with two other unidentified minor products).
(1R,2R,3S,3aS,4R,9bR)-1-Benzyloxy-4-benzyloxymethyl-2,3-isopropylidenedihydroxy-6,8- dimethyl-2,3,3a,4,6,9b-hexahydro-1H-5-oxa-6,8-diaza-cyclopenta[a]naphthalene-7,9-dione (16). Oil; Rf: 0.38 (50% ethyl acetate in hexanes); IR (neat, mixture of products): 3050, 3010, 2960, 2850, 1700-1640 (broad) cm-1; 1H NMR (signal set of major isomer, 16, 300 MHz, CDCl3): 7.42 (d, J = 7.2 Hz, 2H), 7.38-7.29 (m, 7H), 7.27-7.22 (m, 1H), 4.89 (d, J = 11.9 Hz, 1H), 4.73 (d, J = 11.9 Hz, 1H), 4.63 (bs, 2H), 4.57 (dd, J = 7.4, 4.9 Hz, 1H), 4.47 (d, J = 4.7 Hz,
