Studies toward the syntheses of pluramycin natural products. The first total synthesis of isokidamycin

Abstract

We report the first total synthesis of the complex C-aryl glycoside isokidamycin, the epimer of the naturally-occurring pluramycin antibiotic kidamycin. The synthesis features a highly efficientDiels-Alder reaction between a substituted naphthyne and a glycosylatedfuran to form the anthracene core bearing a pendant angolosamine C-glycoside. The regiochemical outcome of the Diels-Alder reaction was controlled by employing a disposable silicon-tether to link the reactive napthyne and the glycosyl furan, rendering the cycloaddition intramolecular. The benzopyranone moietyof the aromatic nucleus was appended by cyclization of a functionalized vinylogous amide onto an advanced anthrol intermediate. The vancosamine amino glycoside was introduced by an O→C-glycoside rearrangement that produced the β-anomer. Subsequent refunctionalizations then led to isokidamycin.

Structure‐activity relationship studies on naphthoquinone analogs. The search for new herbicides based on natural products

“…Modifications carried out at position 5 of the naphthoquinone backbone were made using the corresponding side‐chain and silver(I) oxide. Derivatives 16 – 19 and 21 were synthesized according to the methodology described by O'Keefe et al and derivative 20 was prepared according to the procedure reported by Tietze et al with some modifications, as described above. These compounds were obtained in moderate‐high yield (24–83%) (Fig.…”

“…The use of N , N ‐dimethylformamide (DMF) as solvent led to a considerable improvement in the yield. Derivatives 22 , 23 , 25 – 27 , 32 and 33 were obtained by following the methodology described by O'Keefe et al with different reaction times to ensure completion under reflux. The products were obtained in moderate yields (11–47%).…”

Natural Products and Their Mimics as Targets of Opportunity for Discovery

“…21 This important family of compounds has long attracted interest because of their broad range of biological activities and their resistance to enzymatic hydrolysis. Some C -aryl glycosides that were of interest included galtamycinone 22 and vineomycinone B 2 methyl ester, 23 two representative members of the Group II C -aryl glycosides, 5-hydroxyaloin A, 24 a Group I C -aryl glycoside, as well as kidamycin and its isomer isokidamycin, 25 which belong to the Group III C -aryl glycoside family (Figure 3 ) .…”

“…25 Toward this end, the first stage of the synthesis involved making the glycosyl furan 88 from the known carbohydrate derivative 87 , which was prepared from d -rhamnal according to the protocol reported by Brimble. 34 Refunctionalization of 88 led to 89 , and introduction of the silyl tethering group to give 90 followed previous work (see Scheme 18).…”

Studies Toward the Total Synthesis of Pluraflavin A

“…[5] Notably, the Martin group disclosed their synthesis of the glycosylated pluramycin, isokidamycin ( 3 ), which featured the application of a benzyne–furan cycloaddition to append the C -glycosidic residue. [6] …”