Macrocycles lactams

First the protected oligopeptide is coupled with polymer-bound nitrophenol by DCC. N"-Deblocking leads then to simultaneous cycliiation and detachment of the product from the polymer (M. Fridkin, 1965). Recent work indicates that high dilution in liquid-phase cycli-zation is only necessary, if the cyclization reaction is sterically hindered. Working at low temperatures and moderate dilution with moderately activated acid derivatives is the method of choice for the formation of macrocyclic lactams (R.F. Nutt, 1980). 

The "zip-reaction (U. Kramer, 1978, 1979) leads to giant macrocycles. Potassium 3- ami-nopropyl)amide = KAPA ( superbase ) in 1,3-diaminopropane is used to deprotonate amines. The amide anions are highly nucleophilic and may, for example, be used to transam-idate carboxylic amides. If N- 39-atnino-4,8,12,16,20,24,28,32,36-nonaazanonatriacontyl)do-decanolactam is treated with KAPA, the amino groups may be deprotonated and react with the macrocyclic lactam. The most probable reaction is the intramolecular formation of the six-membered ring intermediate indicated below. This intermediate opens spontaneously to produce the azalactam with seventeen atoms in the cycle. This reaction is repeated nine times in the presence of excess KAPA, and the 53-membered macrocycle is formed in reasonable yield. 

WASSERMANN BORMANN Maciocydiclactamsynttwsis Ring expansion sequence of lactams by reaction with cyclic Iminoethers followed by reductive ring opening to a macrocyclic lactam. 

Amfidinolides (unique macrolides from marine dinoflagellates) 97H(44)543. Antitumor N-, N,S-, and S-heterocycles and macrocyclic lactams from ascidi-ans 97M122. 

This lactamization process can be promoted by enzymes such as pancreatic porcine lipase. Reduction of co-azido carboxylic acids leads to macrocyclic lactams. Although treatment of carboxylic acids with amines does not directly give amides, the reaction can be made to proceed in good yield at room temperature or... 

Macrocyclic lactam alkaloids Verbascum phoeniceum SiOj AcOEt + MeOH T + EtOH 254 nm r. Dragendorff s Identification 22... 

Macrocyclic lactams making use of the double reaction of bisimidazolides — in this case, prepared from the corresponding dicarboxylic acids by in-situ reaction with C6H5POIm2 - were obtained in acceptable yield considering the unfavorable ring sizes of the products 1-1295... 

Wasserman, H. H. (1987). New methods in the formation of macrocyclic lactams and lactones of biological interest. Aldrichimica Acta 20, 63—74. 

As Scheme 97 shows, employing macrocyclic lactams 263 and o-azidoben-zoyl chloride, 4(3//)-quinazolinones (264) are obtained with the aid of an aza-Wittig strategy. Reductive cleavage of the C-2 —N-3 bond of quinazo-... 

Bacterial metabolites include novel alkaloids, peptides, and macrocyclic lactams. The most unusual metabolites from dmoflagellate are polyethers, both linear and macrolides. The latter were also found abundantly in brown seaweeds (Chart 7.6.FA/PO). Filamentous fimgi have afforded new isoindole and quinazoline alkaloids, as well as new-skeleton steroids (Chart 7.6.A/P/I). 

Many macrocyclic lactams have potent physiological activity. Daesung Lee of the University of Wisconsin has taken advantage (Organic Lett. 2004, 6,4351) of the conformational preference of diacyl hydrazides such as 8 to prepare, by Grubbs cyclization of 8 and then again of 10, the 8-8 system 11. Exposure of 11 to Na in liquid ammonia reduced the N-N bond and opened the epoxide, to deliver macrocyclic lactam 12. 

In search of a macrocyclic lactam able to bind p-benzoquinone, Hunter [37] reacted (Figure 26) isophthaloyl chloride 75 with the diamine 76 in the presence of EtaN in CH2Cl2. The resulting diamine 77 was reacted with isophthaloyl chloride... 

Macrocyclic lactams.1 These lactams have generally been prepared by reaction of dicarboxylic acid chlorides and diamines under high dilution. Yields are generally mediocre because linear polyamides are also formed. Actually, free dicarboxylic acids, when activated by diphenylphosphoryl azide, can condense with diamines to... 

Gunasekera, S. P, Gunasekera, M., and McCarthy, P. J., Discodermide a new bioactive macrocyclic lactam from the marine sponge Discodermia dissoluta, J. Org. Chem., 56, 4830, 1991. 

Diphenylphosphoryl azide (DPPA) 58 was first introduced as a reagent for peptide synthesis by Yamada in 197233 and has been widely used since it gives good yields and very little racemization. It may also be used to bring about a modified Curtius reaction in which a carboxylic acid, R CC H and an alcohol, R2OH, react in the presence of triethylamine to afford the carbamate R1 NHCO2R2.33 In Protocol 15, the use of DPPA to form a macrocyclic lactam 61 is illustrated. The 82% yield of the product using this method should be compared with the value of 24% for reaction of the bis(acid chloride) of 59 with the diamine 60. 

Baker and Castro [69 e] reported that DCC, DPP A, or DPEC did not induce the macrocyclic lactam closure in the synthesis of the antitumor antibiotic ( + )-macbecin I, but it was achieved by mesitylenesulfonyl chloride. 

Collum DB, Chen S-C, Ganem B. A new synthesis of amides and macrocyclic lactams. J. Org. Chem. 1978 43 4393-4394. 

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