Aglycone

Ananas comosus (Stickm.) Merr. (Bromeliaceae) [1]. Mp 194-197.5°C (from MeOH), +4.23° 

Kusano, M. Shibano, G. Kusano, T. Miyase, Chem. Pharm. Bull. 44(11), 2078-2085 (1996) 

Taxonomy Cycloartane Triterpenoids Astragalus alopecurus Pall. (Leguminasae) [1]. Astragalus ephemerotorum Gontsch. (Leguminasae) 

Taxonomy Cycloartane Triterpenoids Actea racemosa (Ranunculaceae) [1]. 

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The cyclized products 393 can be prepared by the intramolecular coupling of diphenyl ether or diphenylamine(333,334]. The reaction has been applied to the synthesis of an alkaloid 394[335]. The intramolecular coupling of benzoyl-A-methylindole affords 5-methyl-5,10-dihydroindenol[l,2-b]indol-10-one (395) in 60% yield in AcOH[336]. Staurosporine aglycone (396) was prepared by the intramolecular coupling of an indole ring[337]. 

Antineoplastic Drugs. Cyclophosphamide (193) produces antineoplastic effects (see Chemotherapeutics, anticancer) via biochemical conversion to a highly reactive phosphoramide mustard (194) it is chiral owing to the tetrahedral phosphoms atom. The therapeutic index of the (3)-(-)-cyclophosphamide [50-18-0] (193) is twice that of the (+)-enantiomer due to increased antitumor activity the enantiomers are equally toxic (139). The effectiveness of the DNA intercalator dmgs adriamycin [57-22-7] (195) and daunomycin [20830-81-3] (196) is affected by changes in stereochemistry within the aglycon portions of these compounds. Inversion of the carbohydrate C-1 stereocenter provides compounds without activity. The carbohydrate C-4 epimer of adriamycin, epimbicin [56420-45-2] is as potent as its parent molecule, but is significandy less toxic (139). 

Fig. 1. Stereostmeture of teicoplanin aglycone [89139-42-4] obtained from a Dreiding model (83) where is hydrogen, is nitrogen, O is carbon, is...

Stevioside and rebaudioside A are diterpene glycosides. The sweetness is tainted with a bitter and undesirable aftertaste. The time—intensity profile is characteristic of naturally occurring sweeteners slow onset but lingering. The aglycone moiety, steviol [471 -80-7] (10), which is the principal metaboHte, has been reported to be mutagenic (79). Wide use of stevia ia Japan for over 20 years did not produce any known deleterious side effects. However, because no food additive petition has been presented to the FDA, stevioside and related materials caimot be used ia the United States. An import alert against stevia was issued by the FDA ia 1991. In 1995, however, the FDA revised this import alert to allow the importation and use of stevia as a diet supplement (80), but not as a sweetener or an ingredient for foods. Several comprehensive reviews of stevia are available (81,82). 

The few macrolides having 12-membered rings are Hsted in Table 2. Methymycin (12, R = OH, R = H), isolated from culture broths of a Streptomjces species (29), was the first macroHde stmcture elucidated (30). It is comprised of the aglycone methynolide (13, R = OH, R = H) and the aminosugar desosamine (1, R = OH, R = H) (31,32). Methymycin was also the first conventional macroHde made by total synthesis (33). 

Neomethymycin (12, R = H, R = OH), an isomer co-produced with methymycin, is the product of hydroxylation at C-12 rather than C-10 of the lactone (34,35). The corresponding aglycone, neomethynoHde (13, R = H, R = OH), was isolated with methynolide from broths of S. vene elae (36). The stereochemistry of 12(R)- for neomethynoHde was estabHshed by total synthesis (37). YC-17 (12, R = R = H), also found in broths of S. vene elae is a possible precursor of methymycin and neomethymycin. The hydroxyl groups at C-12 and C-10 are probably added as late steps in the biosynthesis (38). 

Erythromycins. Erythromycin A (14, R = OH, R = CH3, R" = H), the most widely used macroHde antibiotic, was the principal product found in culture broths of Streptomjces eTythreus (39), now reclassified as Saccharopoljspora eythraea (40). It contains a highly substituted aglycone, erythronoHde A, (16, R = R = OH) to which desosamine (1, R = OH, R = H) and cladinose (8, R = CH ) are attached (41). The complete stereochemistry of erythromycin A was estabUshed by x-ray analysis of its hydroiodide dihydrate (42) total synthesis of erythromycin A was a landmark achievement (43), a task previously considered hopeless (44). 

Chemical degradation of erythromycin A yielded its aglycone, erythronoHde A (16, R = R = OH), whereas erythronoHde B (16, R = H, R = OH) was obtained from fermentation (63,64). Biosynthesis of erythromycin proceeds via 6-deoxyerythronoHde B (16, R = R = H) and then erythronoHde B (64,65). The first total synthesis of erythromycin-related compounds was erythronoHde B (66) syntheses of erythronoHde A and 6-deoxyerythronoHde B soon foUowed (67,68). 

Oleandomycin. Oleandomycin (17, R = CH ) was the primary factor in culture broths of S. antihioticus (69,70). Its aglycone, oleandoHde... 

Pikromycin. Pikromycin (19, R = OH, R = H), the first macroHde discovered (77,78), is produced by S.felleus. Pikromycin is identical to amaromycin and albomycetin (79—81) and may be identical to proactinomycin (82—84). The stmcture of pikromycin was deterrnined from chemical degradation, mass spectrometry, nmr, and x-ray crystallography (85—90). Its aglycone, pikronoHde (20, R = OH), was produced by S. vene elae (36). A derivative, kromycin (22, R = OH), was formed from pikromycin under acidic conditions (87,88,91) and more drastic conditions produced an intramolecular spHoketal of pikronoHde named kromin (89,91). 10,11 -Oihydropikromycin (21, R = OH, R = H), was also produced by S. vene elae (92). 

Natural Products. 16-Membered macroHdes are divided into leucomycin- and tylosin-related groups, which differ in the substitution pattern of their aglycones. Multi-factor complexes are usually produced and some compounds have been isolated from culture broths of different organisms and then been given different names. 

A few neutral 16-membered macroHdes have been isolated. The stmcture of chalcomycin (54, R = CH3, R = OH), produced by S. bikiniensis was estabhshed as a 16-membered lactone having two neutral sugars, D-chalcose (7) and D-mycinose (9, R = R = OH3) (293—295). Its aglycone resembles that... 

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