Natural anthracyclines

In natural anthracyclines the sugars are linked hy a-glycosidic linkages, the corresponding 8-glycosides were found to he inactive [49]. L-arabino analogues of daunomycin and doxorubicin, 4 -epidaunomycin and 4 -epidoxorubicin (38), were shown to have similar activity to the natural anthracyclines, the latter (38) also has a lower cardiotoxicity and is now used clinically [50] (O Scheme 15). 

PRODRUGS OF NATURAL ANTHRACYCLINES SUITED FOR ANTIBODY DIRECTED ENZYME PRODRUG THERAPY (ADEPT) AND PRODRUG MONOTHERAPY... 

THP-Protected lactamide 459 has been used to synthesize (2R, 3 S)-2,3-(cyclohex-ylidenedioxy)butanal (462), a key intermediate for the synthesis of L-daunosamine, the amino sugar component of natural anthracycline antibiotics [85] (Scheme 66). The crucial reaction in the sequence is the yw-selective hydrosilane/fluoride reduction of ketone 460, which... 

Table 1 UV data (MeOH) of the six chromophore types found in natural anthracyclines the numbering system of anthraq clines is used...

Only two natural anthracyclines with protons in 6,11-positions were described about 20 are monohydroxylated at C-11, and about 200 are... 

Tables List of natural anthracyclines, according to AntiBase [92], All sugars are connected with the aglycone as 0-glycosides via oxygen... 

To map the set of anthracyclines that can potentially be produced by biosynthetic means, we start with the substituents actually present in natural anthracyclines (Struct. 1) [2] ... 

The possibiUties of attaching a sugar imit by a modified Marshalk reaction [106] were explored by Shaw et al. [107] as the first step on the route to the anthracyclinones fuUy substituted in ring A. The occurrence of the natural anthracyclines aranciamycin and steffimycin [7], fully substituted with oxygen functions and a methyl group at C-9 in ring A, was an incentive to use the... 

When we embarked on the synthesis of anthracyclinones, our goal was to develop a strategy that would allow one to prepare not only the aglycones of natural anthracyclines but also a large variety of modified derivatives. Our methodology had thus to be highly versatile, meaning short and tolerant as far as the nature and the number of substituents that could be introduced... 

Despite all these studies, the first synthesis of a natural anthracycline modified at position 9 with the introduction of a fluoro atom was shown in... 

Natural anthracyclines such as doxorubicin present a carbonyl group on C-13. This is very important for anthracycline toxicity studies, because this group, after biological reduction in vivo, gives the 13-hydroxy derivative that proves to be more cardiotoxic [40]. 

Natural anthracycline analogs isolated from Streptomyces sp. often contain two or more sugars connected by axial (l->4) linkage. The anthracycline disaccharides or oligosaccharides invariably possess amino sugar as the first moiety attached to the aglycon (38,56). For instance, daunosaminyl daunorubicin (Figure 6), which is isolated from fermentation, contains two... 

Most natural anthracyclines contain 2 -deoxyhexoses, a structure that lends susceptibility to acid hydrolysis (190). Tsuchiya and Takagi (190) have synthesized 2 -fluoro derivatives in an effort to stabilize the anthracycline in the presence of acids. Their results indicated that 2 -R configuration was required for biological activity, and that substitutions at 3 caused a dramatic decrease in the activity of the 2 -fluoro derivatives (190). 

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