Structure of frenolicin

Abstract

glycinamide. Dry ammonia was bubbled into a stirred suspension of 3.54 g of the S-benzyl-P-mercaptopropionyl-0-benzyl-L-tyrosyl-Lisoleucyl-r.glutaminyl-r.asparaginyl-S-benzyl-L-cysteinyl-L-prolyl-L-leucylglycyl nitrated resin in 150 ml of anhydrous methanol at 0" for 1.5-2 hr (until the solution was saturated with ammonia). The reaction mixture was stirred overnight at 0-4°.26 The methanol and ammonia were removed under aspirator vacuum. Dimethylformamide (200 ml) was added to the dry residue and the suspension was stirred vigorously for 3 hr. The resin was filtered off and washed three times with dimethylformamide.The solvent was removed from the combined filtrate and washings on a rotary evaporator at below 40". The residue was dissolved in 20 ml of dimethylformamide and 15 ml of distilled water was added gradually with stirring. The turbid solution was allowed to stand in the refrigerator overnight. The precipitate was filtered off, washed with ethanol, and dried in cucuo over KOH pellets; yield, 197 mg, mp 234236".A sample was prepared for analysis by reprecipitating twice from a dimethylformamide-water mixture. The compound was filtered off, washed with ethanol, and dried in L'UCUO, over KOH pellets;mp 238-240", [ c Y ]~~D -37.3" (c 0.6, dimethylformamide).Anal. Calcd for C84H15012NllS2: C, 60.8; H, 6.78; N, 12.2.Found: C,60.9; H,6.78; N, 11.9.Deamino-oxytocin. S-Benzyl-P-mercaptopropionyl-0-benzyl-Ltyrosyl -L-isoleucyl -Lglutaminyl -Lasparaginyl-S-benzyl-L-cysteinyl-L-prolyl-L-leucylglycinamide (1 55 mg) was dissolved in 125 ml of stirred boiling liquid ammonia (distilled from sodium in an all-glass apparatus). A fresh sodium stick was introduced and withdrawn when the blue color pervaded the solution. The sodium stick was momentarily introduced intermittently until the blue color persisted for 30 sec. The ammonia was removed by lyophilization at the water pump and the residue was dissolved in 300 ml of 0.03 z trifluoroacetic acid. The p H of the solution was adjusted to 8.0with ammonium hydroxide and an excess of 0.1 N potassium ferricyanide (4.5 ml) was added to the stirred solution. After 15 min AG 3-X4 resin (chloride form) was added and stirring was continued for 15 min to remove ferrocyanide and excess ferricyanide ions. The resin was removed by filtration, and the solution was lyophilized.The lyophilized residue was dissolved in 20 ml of the upper phase of the solvent system 1-butanol-benzene-3.5 aqueous acetic acid 49 mg (41 z).(25) Ammonolysis conditions as described to us by Dr. Maurice Manning in a personal communication.(26) 0.Abstract: Evidence is put forward which describes the structure and stereochemistry of frenolicin as I.he isolation and preliminary characterization of

Frenolicins C–G, Pyranonaphthoquinones from Streptomyces sp. RM-4-15

“…RM-4-15. Addition of 18 mg/L scandium chloride in a parallel fermentation of the same strain revealed a new compound ( 5 ) along with two the additional known compounds deoxyfrenolicin ( 9 ) 15–17 and UCF 13 ( 10 ). 19 Interestingly, compound 8 and 9 both eluted at the identical retention time and possessed identical UV characteristics (Figure S46).…”

“…15, 17, 20–22 Frenolicin B ( 7 ) was recently identified as a putative AKT-selective kinase inhibitor while UCF76-A ( 8 ) was reported to inhibit Ras p21 farnesylation. 18,23–26 Inspired by the putative anticancer mechanisms reflected within these recent studies, we compared new analogues ( 1 – 5 ) and the known frenolicins ( 6 – 10 ) in a standard cancer cell line cytotoxicity assay using the human non-small cell lung carcinoma A549.…”

Dimeric Pyranonaphthoquinones: Isolation, Bioactivity, and Synthetic Approaches

“…This was established by extensive spectral analysis. [75][76][77][78][79] Frenolicin G (8) has a symmetrical dimer structure and contains a frenolicin core with a thioether bridge at the 4a-position. Thorson and co-workers recently identified the new Sbridged dimeric pyranonaphthoquinone frenolicin G [74] (8) along with the additional known compounds frenolicins C-F ( Figure 10).…”

Functional replacement of genes for individual polyketide synthase components in Streptomyces coelicolor A3(2) by heterologous genes from a different polyketide pathway

“…represents a system favorable for answering these questions. Several compounds of this structural type, including actinorhodin (Streptomyces coelicolor) (10), granaticin (Streptomyces violaceoruber) (30), frenolicin (Streptomyces roseofulvus) (6), and griseusin * Corresponding author.…”