(−)-Pseudodistomin E: First Asymmetric Synthesis and Absolute Configuration Assignment

Abstract

(-)-Pseudodistomin E has been prepared for the first time, allowing its structure and absolute configuration to be confirmed. The established conjugate addition of lithium (S)-N-allyl-N-(α-methyl-p-methoxybenzyl)amide to methyl (E,E)-hepta-2,5-dienoate generated the C(2)-stereocenter, and iodolactonisation of a derivative generated the remaining two stereogenic centers. Ensuing iodide displacement was achieved using a tethering strategy, to introduce the nitrogen atom to C(5). Decarboxylative coupling of a carboxylic acid with a dialkylzinc reagent completed construction of the tridecadienyl chain.

Marine natural products

“…Further work is required to clarify these ndings. The structures of a number of NPs have been conrmed by total synthesis including halocyamine A, 664 biselides A 665 and E, 666 ningalin G, 667 (+)-arborescidine C, 668 and (À)-pseudodistomin E. 669 Absolute conguration was assigned to the phosphorylated polyketide phospoeleganin (Sidnyum elegans) by synthesis of model fragment alicyclic compounds and their cyclic derivatives, and comparison of 1 H and 13 C NMR chemical shis. 670 Improved semisyntheses of ecteinascidin 743 and (À)-jorumycin from safracin B have been reported.…”

The Hancock Alkaloids (−)-Cuspareine, (−)-Galipinine, (−)-Galipeine, and (−)-Angustureine: Asymmetric Syntheses and Corrected 1H and 13C NMR Data

“…Reduction of 34 using Raney-Ni in a mixture of EtOH and THF for 1 h effected complete desulfurization to give predominantly 35, although partial Ndebenzylation was also evident; when the reaction was left to run for extended time periods, hydrogenation of the aromatic ring also occurred (in addition to N-debenzylation). Thus, the crude reaction mixture was subjected to the conditions successfully employed for one-pot hydrogenolytic N-debenzylation and reductive N-methylation in the synthesis of the other alkaloids, which in this case gave (−)-angustureine (36) in 69% yield from 34, corresponding to 39% yield over nine steps from commercially available 3-(o-bromophenyl)propanoic acid 6 (Scheme 11).…”

“…The absolute configuration at the newly formed C-3 stereogenic center of (3 R ,α R )- 14 was assigned by reference to the transition state mnemonic that we have developed to predict the stereochemical outcome of this class of conjugate addition reactions . Subsequent treatment of (3 R ,α R )- 14 with HCO 2 H in the presence of Et 3 SiH − effected chemoselective removal of the N -α-methyl- p -methoxybenzyl group to furnish ( R )- 15 in 81% yield (Scheme ).…”

“…Conjugate addition of lithium ( S )- N -benzyl- N -(α-methyl- p -methoxybenzyl)­amide ( S )- 11 to α,β-unsaturated Weinreb amide 9 gave β-amino amide (3 S ,α S )- 14 as a single diastereoisomer (>95:5 dr), in 99% yield. Chemoselective removal of the N -α-methyl- p -methoxybenzyl group from (3 S ,α S )- 14 using HCO 2 H in the presence of Et 3 SiH − gave ( S )- 15 in 80% yield. Finally, intramolecular Buchwald–Hartwig coupling provided ( S )- 16 quantitatively (Scheme ).…”

Metathesis Reactions in Natural Product Fragments and Total Syntheses

“…These molecules are organized under various transformations in the following sequence: 1) ring‐closing metathesis, 2) cross metathesis, 3) ring‐closing alkyne metathesis, and 4) ring‐closing enyne metathesis. 1) Ring‐closing metathesis : kanamienamide ( 37 ), [100] (+)‐chinensiolide B ( 38 ), [101] BMS‐846372 ( 39 ), [102] daphniyunnine B core ( 40 ), [103] clavilactone D ( 41 ), [104] pechueloic acid ( 42 ), [105] (−)‐deoxoapodine ( 43 ), [106] zephyranthine ( 44 ), [107] palodesangrens core ( 45 ), [108] (−)‐stemaphylline ( 46 ), [109] pavidolide B ( 47 ), [110] 7‐deoxypancratistatin ( 48 ), [111] (+)‐4‐ ɑ ‐dehydroxycrinamabine ( 49 ), [112] (−)‐elymoclavine ( 50 ), [113] viridin ( 51 ), [114] (−)‐crinane ( 52 ), [112] conduramine B‐1( 53 ), [115] ellipticine quinone ( 54 ), [116] (−)‐tegafur ( 55 ), [117] tetraponerine ( 56 ), [118] (−)‐cermizine B ( 57 ), [119] (Figure 7) (±)‐lycojaponicm ( 58 ), [120] (−)‐zeylenol ( 59 ), [121] aphanamal ( 60 ), [122] (+)‐epiquinamide ( 61 ), [123] erythrinane core ( 62 ), [124] (−)‐pseudodistomin E ( 63 ), [125] toxicodenane A ( 64 ), [126] ipomoeassin F ( 65 ), [127] scholarisine K ( 66 ), [128] panal core ( 67 ), [129] (+)‐crotanecine ( 68 ), [130] gagunin E analogue ( 69 ), [131] R‐(−)‐ ɑ ‐cuparenone ( 70 ), [132] citreamicin‐η core ( 71 ), [133] brianthein A core ( 72 ), [134] (+)‐cryptoconcatone H ( 73 ), [135] neomarchantin A ( 74 ), [136] (+)‐methynolide ( 75 ), [137] 10‐epi‐tirandamycin ( 76 ), [138] greensporone C ( 77 ), [139] 5′‐hydroxy‐zearalenone ( 78 ), [140] cheloviolene A ( 79 ), [141] crassifoside F c...…”