Echinocandin synthesis

Echinocandins (i.e. caspofungin), semisynthetic lipo-peptides, inhibits the synthesis of (3-(l,3)-D-glucan, an... 

Synthesis of deuteriated and tritiated echinocandin B and anilinostearamide and the problem of HPLC isotope effects... 

Pharmacology Micafungin is a semisynthetic lipopeptide (echinocandin) synthesized by a chemical modification of a fermentation product of Coleophoma empetri F-11899. Micafungin inhibits the synthesis of 1,3- -D-glucan, an essential component of fungal cell walls, which is not present in mammalian cells. Pharmacokinetics ... 

Echinocandins act at the level of the fungal cell wall by inhibiting the synthesis of B(l-3)-glucan (Figure 48-1). This results in disruption of the fungal cell wall and cell death. 

One example of the utilization of this approach for the synthesis of natural products is the facile access, Fig. 10, to the southwest tripeptide segment of echinocandin B, 148, a cyclic hexapeptide that is characterized by its antifungal and antiyeast activity. 

M Tomishima, H Ohki, A Yamada, El Takasugi, K Maki, S Tawara, El Tanaka. FK463, a novel water-soluble echinocandin lipopeptide synthesis and antifungal activity. J Antibiot 52 674-676, 1999. 

M Debono, BJ Abbott, DS Fukuda, M Barnhart, KE Willard, RM Molloy, KM Michel, JR Turner, TF Butler, AH Hunt. Synthesis of new analogs of echinocandin B by enzymatic deacylation and chemical reacylation of the echinocandin B peptide synthesis of the antifungal agent cilofungin (LY121019). J Antibiot 42 389-397, 1988. 

M Debono, BJ Abbott, JR Turner, LC Howard, RS Gordee, AS Hunt, M Barnhart, RM Molloy, KE Willard, DS Fukuda, TF Butler, DJ Zeckner. Synthesis and evaluation of LY121019, a member of a series of semisynthetic analogues of the antifungal lipopeptide echinocandin B. Ann NY Acad Sci 544 152-167, 1988. 

JA Jamison, DJ Zeckner, MJ Rodriguez. The synthesis and antifungal activity of V-alkylated analogs of echinocandin B. J. Antibiot 50 562-566, 1997. 

Initial modification of the acyl side chain yielded FR131535.11 The synthesis of this novel echinocandin-like lipopeptide is outlined in Figure 15.5. The palmitoyl group was removed from FR901379 by treating it with acylase from Actinoplanes utahensis, which yielded FR179642. A new acyl side chain was prepared starting with 1-bromooctane and 4-hydroxybenzoic acid. 

Kurokawa and Ohfune [71] employ i DPPA in the synthesis of the hexapeptide echinocandin D 125). As shown in Scheme 42, the cyclization of the Unear peptide 124 was accomplished by DPPA to give 125 in 50% yield. There are more applications of DPPA in the synthesis of macrocycUc natural products [72]. DEPC is relatively less commonly used than DPPA. Kishi and coworkers [73] have successfully achieved the synthesis of the macrocyclic antibiotic rifamycin S using DEPC as a macrolactamization promoter. 

The fungal metabolite echinocandin B (118)is one of the lipopeptides, in which a cyclic hexapeptide is combined with a long-chain fatty acid. Echinocandin B inhibits jS-l,3-glu-can synthesis and as a result has anti-Candida and anti-Pneumocystis carimi activity (149). As a group, the echinocandins are not orally bioavailable, are haemolytic, and are not very... 

Synthesis of the cyclic hexapeptide echinocandin D (256) involves a key intermediate tetrapeptide 255 which is prepared from 253 and AMinoleyl-N-Boc ornithine (254) using DEPC.95 Echinocandin D, isolated from Aspergillus ruglosus, is a member of a family of lipopeptides possessing high antifungal activity. 

Balkovec, J.M., Black, R.M., Hammond, M.L., etal. (1992) Synthesis, stability, and biological evaluation of water-soluble prodrugs of a new echinocandin lipopeptide. Discovery of a potential clinical agent for the treatment of systemic candidiasis and Pneumocystis carinii pneumonia (PCP). J. Med. Chem. 35 194-198. 

Intramolecular reaction of the organoborane with an azide provides a cyclic amine product. For example, in a synthesis of the cyclic hexapeptide echinocandin D, stereoselective hydroboration of the alkene 19 was followed by cyclization to give the substituted pyrrolidine 20 (5.28). ... 

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