(−)-(3S)-3-(Tosylamino)butano-4-lactone, a Versatile Chiral Synthon for the Enantioselective Synthesis of Different Types of Polyamine Macrocycles: Determination of the Absolute Configuration of (−)-(R)-Budmunchiamine A

Abstract

À)-(3S)-3-(Tosylamino)butano-4-lactone (1) and its derivative ethyl (À)-(3S)-4-iodo-3-(tosylamino)butanoate (2) are presented as easily accessible chiral building blocks for the construction of a range of different macrolactam frameworks important for the synthesis of naturally occurring polyamine alkaloids as well as for establishing a substance library of such compounds, including S-containing derivatives for biological tests. In addition to that, the absolute configuration of the spermine alkaloid (À)-(R)-budmunchiamine A (3) from Albizia amara was determined by total synthesis according to the new methodology.Scheme 2 a) PPh 3 , 1H-imidazole, I 2 , CH 2 Cl 2 , r.t., 1 h; 89%. b) t BuLi, Et 2 O, À 788 3 r.t., 2 h. c) CuBr ¥ Me 2 S, Et 2 O/THF, À 788 3À 208, 30 min. d) 2, Et 2 O/THF, À 608 3À 108, 3 h; 75%. e) H 2 N(CH 2 ) 4 NH 2 (10), Cu(OAc) 2 , r.t., 8 h; quant. f) TsCl, Et 3 N, CHCl 3 , r.t, 2 h; 93%. g) TsO(CH 2 ) 3 OTs (13), Cs 2 CO 3 , DMF, 658, 24 h, 78%.h) Electrolysis, EtOH, 58; 92%. Figure. ORTEP [14] Plot of the doubly N-tosylated macrolactam 14

Total Synthesis of the Anti‐inflammatory and Pro‐resolving Lipid Mediator MaR1n−3 DPA Utilizing an sp3–sp3 Negishi Cross‐Coupling Reaction

“…A Swern oxidation of 14 produced multi‐grams of TBS‐protected 3‐hydroxy‐4‐pentynal ( 15 ) in overall 47 % yield (Scheme ). The Wittig salt 9 was prepared from cis ‐3‐hexen‐1‐ol ( 16 ) in 90 % yield using a literature procedure21 (see Scheme ). Then a Z ‐selective Wittig reaction between 9 and aldehyde 15 afforded alkyne 6 in 83 % yield after purification by chromatography.…”

Polyamine alkaloids

“…53 However, the absolute configuration of (−)-(R,R)-hopromine, one of its major alkaloids, has only been established recently by an enantioselective synthesis by Ensch et al 54 This enantiospecific synthesis of hopromine not only provided the nature-identical alkaloid, but gave, via the chiral non-racemic intermediate 11, stereoselective access to a range of other cyclic polyamine alkaloids, such as the budmunchiamines. 51 The enantiospecific preparation of (−)-(R,R)-hopromine started from enantiomerically pure L-aspartic acid (9, Scheme 2). This amino acid was initially converted to its N-tosyl derivative, which gave upon treatment with thionyl chloride the corresponding succinic anhydride product.…”

Total Synthesis of the Anti‐inflammatory and Pro‐resolving Lipid Mediator MaR1n−3 DPA Utilizing an sp3–sp3 Negishi Cross‐Coupling Reaction

“…A Swern oxidation of 14 produced multi-grams of TBS-protected 3-hydroxy-4-pentynal (15) in overall 47% yield (Scheme 1). The Wittig-salt 9 was prepared from cis-3-hexen-1-ol (16) in 90% yield using a literature procedure, [21] see Scheme 1. Then a Z-selective Wittig reaction between 9 and aldehyde 15 afforded alkyne 6 in 83% yield after purification by chromatography.…”