C-13 keto group

Santavy et al. studied the UV spectra to establish whether in 13-oxopro-topine alkaloids (121) the interaction of the tertiary nitrogen may also take place with the oxo group at C-13 (420). It was found that this interaction takes place only with the keto group at C-14. Such an interaction does take place if only a C-13 keto group (120b) is present (674). In protopine and cryptopine, the nature of intramolecular N - C=0 interactions were measured by X-ray crystallography (689). 

Interesting observations have been made by Witt et al.m upon replacement of Thr(A739) in C. reinhardtii. This amino acid is hydrogen bonded to the 13 -keto group of PA. The ENDOR spectra showed clear changes of the major hfcs. In contrast to the histidine mutants, the hfcs are decreased. A similar mutant, TA(A739), has also been shown to have different g-tensor components than WT in C. reinhardtii. 95... 

Variants at the C-9 substituent can be divided into 3 main groups, derivatives at the C-13 keto function, derivatives at the C-14 hydroxy group and compounds with an inverted configuration at C-9. The only known compounds of the latter type are 7,9-diepimers and these have already been discussed. Before considering the other 2 groups, there are 2 compounds which do not fit into either group, these are the acid (96) formed by periodate oxidation of adriamycin and the... 

Derivatives at the C-13 keto function Derivatives at the C-14 hydroxyl group Comments... 

Confirming the importance, for the biological activity,10-n of a keto group in the sugar moiety, the antiviral activity of some keto-C-nucleo-sides has also been reported.13 From this study, it was clear that the presence of a ketone group in these nucleosides, as in 4 -ketonucleoside 50a, gave a compound able to inhibit the replication of murine leukemia virus at nontoxic concentrations. 

The electrophilic component in these co-cyclisation reactions can bear other functionality. For example, reaction of isobutenyl dichloride 10 with the appropriate linear dithiols gives good yields of polythiacycles such as 11, 12 and 13.11 A related reaction allows the direct introduction of a keto group into such poly-thia macrocycles. The electrophilic component in this case is 1,3-dichloropropanone, 14. The reaction conditions (Cs2C03, DMF, 60 °C), are insufficiently basic to induce a Favorskii reaction. Furthermore, under the aprotic, basic conditions, thioketal formation cannot take place, allowing successful co-cyclisation to be undertaken, such as in the formation of 15 (Scheme 3.4). Similar reactions allow the preparation of 16,17 and 18.11... 

In a more recent approach (Scheme 11), Schin-zer solved the problem of the C4-C5 retro-aldol reaction with Braun s (S)-HYTRA (51) [44] by replacing the keto group in /(-ketoaldehyde 49 with a C=C double bond cf. 52, derived in four steps from ethyl-2-bromo-Ao-butyrate and 3-pentanone in 13% overall yield). The thus formed intermediate 53 is later deprotected and cleaved oxidatively to give the desired C5 ketone 7 in 52 % yield and 96 % ee from aldehyde 52 [22]. 

Alkyl and acyl derivatives (28, 30) of 14-aminocodeinones (13, 26) and dihydro-codeinones (20a, 27) are readily prepared acylation is achieved under standard conditions of acid chloride or acid anhydride in the presence of an organic base, while alkylation can be achieved directly with an alkyl halide or by acylation and then lithium aluminium hydride reduction (Scheme 5). In this latter method the 6-keto group is protected as an acetal [8, 9, 18, 19]. For direct alkylation with unactivated alkyl halides, carrying out the reaction in a sealed tube at 120 °C has... 

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