Aglycone precursors coupling

The required furanosylated indolocarbazole 1380 should be readily available by reduction of 1379, a precursor of (+)-K-252a (330). For the synthesis of (+)-K-252a (330) a single-step cycloglycosidation of the selectively protected aglycon 1381 with an appropriate furanose was planned. The protected aglycon 1381 should be readily available by a rhodium-catalyzed coupling of 2,2 -bisindole 1384 with the a-diazo-p-keto-y-lactam 1382 (Scheme 5.232). 

The synthesis of the disaccharides entailed the preparation of 3,6-dideoxyhexosyl (paratosyl, abequosyl and tyvelosyl) precursors suitable for joining to an appropriately derivatized D-mannose residue ( , 10). In order to couple the synthesized disaccharides to carrier proteins it was necessary to have an aglycone containing a suitable reactive group such as a p-isothiocyanatophenyl group... 

Reactions [99] of active methylene nucleophiles other than aldehydes and ketones with carbonyl compounds are also used for cyclizations. An example is the coupling reaction between sulfone and carbonyl. A sulfonyl group is easy to introduce and easy to remove. Yoshii and coworkers [100] used a sulfone-mediated macrocycliza-tion in the synthesis of ( )-0(26)-methyl-28,29-bisnor-kijanolide 171), the aglycone of the antitumor antibiotic kijanimicin. As shown in Scheme 56, treatment of the linear precursor 169 with 1 equiv of sodium r-amylate at room temperature for 10 min. afforded the macrocycle 170 in 82% yield. On the other hand, a diastereoisomer of 169 with opposite configuration at all the stereocenters in the octalin system resisted cyclization under the same conditions. This failure comes from a severe steric hindrance in the transation state of cyclization. Once again, stereochemistry is also an important factor for macrocyclization (cf. Section 2.10). 

In their landmark total synthesis of polyene macrolide Amphotericin B [92], Nicolaou and coworkers designed a mycosamine precursor 57 and coupled it with a highly functionalized aglycon (O Scheme 32). Inversion of the C2-OH followed by the azide reduction and deprotections competed the total synthesis. 

Epicastasterone (13) is assumed to be the immediate biogenetic precursor of 24-epibrassinolide (12), analogously with the related couple castasterone (3) and brassinolide (1) in the (245 )-series. 4 In further experiments 3H labeled 24-epicastasterone (13) was fed to cell suspension cultures of Lycopersicon esculentum and the extract obtained four days after administration was shared into two halfs. One part was subjected to enzymatic hydrolysis (aglycone fraction) while the other one was further used in the glucosidic state. 

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