New Pyrrolizidinone Antibiotics CJ-16,264 and CJ-16,367.

Abstract

Two new antibiotics, CJ-16,264 (I) and "CJ-16,367 (II), were isolated from the fermentation broth of an unidentified fungus CL39457. These antibiotics have a pyrrolizidinone skeleton, first discovered in fungi. Compounds I and II inhibit the growth of Gram-positive multi-drug resistant bacteria and some Gram-negative strains such as Moraxella catarrhalis and Escherichia coll with altered permeability (imp). Comparison of an antibacterial profile between the two compoundssuggested that the gamma-lactone portion of I is important for the activity.

Total Synthesis and Structural Revision of Antibiotic CJ‐16,264

“…The same argument and supporting evidence provided above for corrected- ent - 1 and 32 apply here for (−)- 38 and 40 and their precursors 37 and 39 , respectively. To our delight, the spectroscopic data ( 1 H- and 13 C-NMR) and mass spectrum of structure (−)- 38 were found to be in agreement with the data reported for the natural CJ-16,264, 1 suggesting a structural revision for the antibiotic CJ-16,264. The optical rotation of 38 ([α] D = −9.8° in MeOH), however, was found to be of the opposite sign to that reported for the natural product ([α] D = +27.3° in MeOH) 1 , pointing to the enantiomer of (−)- 38 as the true structure of antibiotic CJ-16,264.…”

“…To our delight, the spectroscopic data ( 1 H- and 13 C-NMR) and mass spectrum of structure (−)- 38 were found to be in agreement with the data reported for the natural CJ-16,264, 1 suggesting a structural revision for the antibiotic CJ-16,264. The optical rotation of 38 ([α] D = −9.8° in MeOH), however, was found to be of the opposite sign to that reported for the natural product ([α] D = +27.3° in MeOH) 1 , pointing to the enantiomer of (−)- 38 as the true structure of antibiotic CJ-16,264. With this information in our possession, we then sought to synthesize the antipode of (−)- 38 , compound (+)- 38 (Scheme 4) in order to fully confirm the absolute configuration and obtain a synthetic sample of the naturally occurring antibiotic CJ-16,264.…”

“…The 1 H- and 13 C-NMR spectroscopic and spectrometric data for synthetic CJ-16,264 matched those reported 1 and provided by Dr. Y. Sugie for the natural product and so did the sign of optical rotation ([α] D = +7.7° in MeOH). Attempts to recrystallize (+)- 38 from a variety of solvents thus far led to partial formation of the C7′-C8′ enol (enol proton, δ = 12.72 ppm, keto:enol ca 4:1) form and semicrystallization.…”

“…The assigned structure of this molecule is intriguing in that it is amongst the most complex of its relatives, CJ-16,367 [ 2 , Figure 1a, stereochemistry unassigned, isolated from the same fungus (CL39457)] 1 , UCS1025A ( 3 , Figure 1a) 2 and UCS1025B ( 4 , Figure 1a) 2 , 21-( S )- and 21-( R )-myceliothermophins C ( 5a ) 3,4 and D ( 5b ) 3,4 (Figure 1b), and the most recently reported antibiotic pyrrolizilactone 5 ( 1a , Figure 1a). Antibiotic CJ-16,264 ( 1 ) possesses a challenging tetramethylated decalin system, whose relative and absolute configurations differ from those of its less complex siblings UCS compounds ( 3 and 4 ), and the myceliothermophins C ( 5a ) and D ( 5b ) (see Figure 1).…”

Microwave-promoted, catalyst-free, multi-component reaction of proline, aldehyde, 1,3-diketone: one pot synthesis of pyrrolizidines and pyrrolizinones

“…5 264 is a class of well-known antibiotics containing a pyrrolizinone skeleton. 6 UCS1025A is also an alkaloid with a pyrrolizinone core that exhibits antimicrobial and anti-proliferative properties as well as telomerase inhibitory activity. 7 In light of their unique structural features along with the important biological activities, the preparations of pyrrolizidines and pyrrolizinones have drawn considerable attention to synthetic chemists in recent years.…”