A Direct and Stereocontrolled Route to Conjugated Enediynes

Abstract

A unified synthetic route to 3-hex-en-1,5-diynes, a key building block found in many of the enediyne antitumor agents and designed materials, was developed. The method, which relies on a carbenoid couplingelimination strategy is tolerant of a wide range of functionalities, and was applied to the synthesis of a variety of linear and cyclic enediynes. Reaction parameters can be adjusted to control stereoselectivity of the process, producing linear enediynes from 1:12 to >100:1 E:Z ratio, and in the case of cyclic enediynes, giving the exclusively Z C-9, C-10, or C-11 products. Key features of the process are the ready availability of precursors and the mildness and efficiency of the reaction. Application of the process in the design of materials precursors and preparation of enediyne antitumor agents are presented.

Rhodium‐Catalyzed Asymmetric Aqueous Pauson–Khand‐Type Reaction

“…The crude product was concentrated and distilled under reduced pressure (b.p. = 88-90 8C, 1 mmHg) to afford 3-bromo-1-phenyl-1-propyne [34] Allylamine (4.0 mL, 53 mmol) was charged into a three-necked roundbottomed flask and freshly distilled diethyl ether (10 mL) was added at room temperature under nitrogen. 3-Bromo-1-phenyl-1-propyne (1.0 g, 5.13 mmol) was added dropwise at 0 8C and the reaction mixture was stirred at room temperature for 2 h. The reaction was quenched with water and extracted with ethyl acetate (3 % 50 mL).…”

Regiospecific, Enantiospecific Total Synthesis of C-19 Methyl Substituted Sarpagine Alkaloids Dihydroperaksine-17-al and Dihydroperaksine

“…13 In order to introduce the desired stereocenter at C-19 into the sarpagan skeleton, the synthesis of the optically active R -acetylenic tosylate 11 was carried out as illustrated in Scheme 1. The racemic TIPS propargylic alcohol 9 was synthesized according to the procedure of Jones et al 14 from commercially available triisopropylsilyl acetylene in 95% yield. The optically active R -propargylic alcohol 10 [enantiomeric ratio (er) = 90:10] was synthesized from 9 via a two step oxidation/ asymmetric hydrogenation sequence under the conditions developed by Marshall et al 15 for the S -propargylic alcohol.…”

A stereo-controlled route to conjugated E-enediynes

“…3-Ene-1,5-diynes are important components of many enediyne antitumor agents and luminescent materials [1]. There are many cis-or trans-fused examples of the enediynes derivatives, such as the recently discovered ten-member antibiotics calicheamicinone 1 [2], the cross-coupling annulus dodecadehydro[18] annulenes 2 [3], and the poly-alkynes nano-tube material 3 [4].…”