Baccharins

Baccharis cordifolia (Compositse). Baccharine, crystalline, neutral to litmus. (Arata, Pharm. J., 1879 [iu], 10, 6.)... 

Baccharis cordifolia baccharine, 779 Bakankosine, 554 Banisteria spp., 488 Banisterine, 488 BapHsia spp., 116 Baptitoxine, 142... 

Drupanin (M.W 232.27), kaempferide (M.W 300.26), artepillin C (M.W 300.39), and baccharin (M.W 364.44) were isolated from Brazilian propolis. Raw propolis was extracted with 90% aqueous ethanol and the extract was fractionated on a reverse phase flash column. The bioactive fractions were subjected to preparative Ci8 HPLC to obtain four major compounds (Supplementary Figure 1). 

Structural comparison of the isolated compounds with spectral data in the literature identified them as drupanin, kaempferide, artepillin C, and baccharin [18, 19, 20, 21], The structures of the four compounds are shown in Figure 1 and Supplementary Figures 1-5. 

The roridin family constitutes another subclass of the trichothecane macrolides. Two examples of this group are roridin E (148) and baccharin Bj (150). The latter is isolated from the plant Baccharis megapotamica and is a potent antileukemic agent. Structurally, this class of compounds is quite similar to the verrucarins discussed above, with the exception of the replacement of the hydroxypentanoic acid-muconic ester linkage by an ether bond and some additional carbon substitution. 

Bioassay-guided fractionation of an alcoholic extract of B. megapotamica, which showed significant activity in vivo against P-388 leukemia in mice and in vitro against cells derived from human carcinoma of the nasopharynx, yielded four potent antileukemic trichothecenes baccharin, Fig. (57), baccharinol, Fig. (58), isobaccharinol, Fig. (59) and isobaccharin, Fig. (60) [84],... 

Kupchan SM, Jarvis BB, Dailey RG, Bright W, Bryan RF, Shizuri Y (1976) Baccharin, a Novel Potent Antileukemic Trichothecene Triepoxide from Baccharis megapotamica. J Amer Chem Soc 98 7092... 

D-Xylose has been used as a starting material for the synthesis of the macrocyclic loop of the anti-leukaemic trichothecanoids baccharin B5 and roridin E, which contains the C-6 and C-13 asymmetric centres. Standard transformations on crystalline... 

To date, only a few total syntheses of trichothecenes have been published, such as the non-macrocycHc trichothecenes trichodermin (375), anguidine (376), and sporol (377). Examples of the synthesis of macrocyclic trichothecenes are for roridin E (378), baccharin B5 (379), and vemicarin A (380) (Fig. 8.4). 

In 1983, Still et al. published methods for the total synthesis of roridin E (378) and baccharin B5 (379) (332). Roridin E (378) was isolated for the first time in 1965 from Myrothecium verrucaria and baccharin B5 (379) was obtained in 1976 from the plant Baccharis megapotamica (333,334). 

Scheme 8.20 Synthesis of precursor 474 for roridin E (378) and baccharin B5 (379). Reagoits and conditions a) DCC, 0.1mol% 4-pyrroUdinopyridine, 95% yield at 55% conversion b) H02CCH2P0(0Me)2, DCC, 4-pyrrolidinopyridine, quant...

For the total synthesis of baccharin B5 (379) six more steps were necessary. First, the alcohol group was protected and then the unconjugated double bonds could be epoxidized selectively to provide 477 as a single product. Subsequently, the epoxide of the macrocycle 477 was eliminated to an allylic double bond, which could be epoxidized again and gave the epimer of baccharin B5. Last, the epimer was converted into baccharin B5 (379) via a Mitsunobu reaction (Scheme 8.21). 

Scheme 8.21 Total synthesis of roridin E (378) and baccharin B5 (379). Reagents and conditions a) TsOH b) NaI04 c) Et3N, MeOH d) Ph3PCH2CHO, 65% over fonr steps, ( ) (Z) = 4 1 e) K2CO3, 18K rown-6, 45% f) t-BuOK, 70% g) TBSOTf, lutidine, 95% h) m-CPBA, 70% i) KOt-Bu, 90% j) t-BuOOH, VO(acac)2, 90% k) HCO2H. DEAD, PPh3. 40% conversion/90% yield 1) TBAF, 99%...

Still WC, Gennari C, Noguez JA, Pearsmi DA (1984) Synthesis of Macrocyclic Trichothecanoids Baccharin B5 and Rraidin E. J Am Chem Soc 106 260... 

C29H33BrC106S, Ascochlorin p-bromobenzenesulphonate, 37B, 337 C29H38O11 X H2O, Baccharin hydrate, 42B, 480... 

In the second structural group, the macrocyclic trichothecenes, the hydroxy groups at C-4 and C-15 of the simple trichothecene skeleton are bridged by a di- or trilactide ribbon. The verrucarins (triesters. Table IV), the roridins (diesters. Table V) and the baccharins (diesters. Table VI) are the major structural subunits of this group. Vertisporin and the satratoxins complete this class, and can be found at the bottom of Table V. Verrucarol (82) is most often the sesquiterpene onto which the macrocycle is attached. Verrucarin K (43) is a notable exception and was the first trichothecene known which lacks the 12,13-epoxide unit. A number of macrocyclic... 

The first report dealing with the synthesis of a macrocyclic tri-chothecene, albeit a non-natural product, originated from Tamm s laboratory in 1978 (22). Three years later, Still and Ohmizu synthesized the first naturally occurring macrocyclic trichothecene verrucarin A (37) (133). Since 1981, the increased availability of verrucarol (82) (150), the sesquiter-penoid backbone for most of the macrocycles, has stimulated work in this area and culminated in Still s recent syntheses (135) of baccharin B5 (59) and roridin E (47), the most complex trichothecenes synthesized to date. Sandwiched between these landmark syntheses have been equally exciting studies initiated by Tamm (verrucarin A and 3a-hydroxyverrucarin A (106), Fraser-Reid and Jarvis (verrucarin J) (42) and Roush (verrucarin J and... 

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