Francisco Bermejo

Production of 3-hydroxy-n-phenylalkanoic acids by a genetically engineered strain of Pseudomonas putida

Overexpression of the gene encoding the poly-3-hydroxy-n-phenylalkanoate (PHPhA) depolymerase (phaZ) in Pseudomonas putida U avoids the accumulation of these polymers as storage granules. In this recombinant strain, the 3-OH-acyl-CoA derivatives released from the different aliphatic or aromatic poly-3-hydroxyalkanoates (PHAs) are catabolized through the β-oxidation pathway and transformed into general metabolites (acetyl-CoA, succinyl-CoA, phenylacetyl-CoA) or into non-metabolizable end-products (cinnamoyl-CoA). Taking into account the biochemical, pharmaceutical and industrial interest of some PHA catabolites (i.e., 3-OH-PhAs), we designed a genetically engineered strain of P. putida U (P. putida U ΔfadBA-phaZ) that efficiently bioconverts (more than 80%) different n-phenylalkanoic acids into their 3-hydroxyderivatives and excretes these compounds into the culture broth.

Suitable entry to a 10-membered ring with eleutheside functionality through Nozaki–Hiyama condensation

Access to a medium-sized unit of 15-seco-eleutheside analog 19 has been opened through the NiCl2/CrCl2-mediated intramolecular condensation of iodoaldehyde 8 with excellent yields. Transformation of the phenylcyclononanol 15 into the tetracyclic analog 19 was achieved in a four-step sequence with 65% overall yield.

Synthesis of azaspiro[4.5]decane systems by oxidative cyclization of olefinic precursors

Abstract The synthesis of 6-benzyloxycarbonyl-1-oxa-6-azaspiro[4.5]decan-2-one ( 17 ) and 6-benzyloxycarbonyl-1,6-diazaspiro[4.5]decan-2-one ( 18 ) from the D,L-pipecolic acid derivative 10 , is described. The synthesis of (±)-6-benzyl-3-methyl-1,6-diazaspiro[4.5]dec-3-ene-2,7-dione ( 29 ), the spiro structural unit of (±)-pandamarine ( 8 ) has been achieved by oxidative cylization of the ( Z ) and ( E ) isomers of 5-(N-benzyl-4-carboxamidobutylidene)-3-methyl-3-pyrrolin-2-one ( 25 ) and ( 26 ). The stereoselectivity obtained in the intramolecular cyclization process has also been discussed.

Decarbonylation of α-tertiary amino acids application to the synthesis of polyhydroxylated indolizidines from D,L-pipecolic acid

Abstract The decarbonylation of the bicyclic α-tertiary carboxamido acid 11 led to the enamide 12, easily transformed into the indolizidine alkaloid 8,8a-trans-8-hydroxy-indolizidine 14. Likewise, the same process applied to the α-substituted pipecolic acid derivative 5 led to the unsaturated ester 6 which was easily transformed either into δ-coniceine 9 or to 14. The thermal fragmentation of the acyl derivative 22 led to the enamide 24 which has been transformed into (±)-swainsonine 26.

Total synthesis of (−)-ampullicin and (+)-isoampullicin two growth regulators from Ampulliferina Sp. No. 27

The growth regulators (−)-Ampullicin (1) and (+)-isoampullicin (2) have been synthesized utilizing carbaldehyde (25) as the chiral source and N-tertbutoxycarbonyl-3-methyl-2-(trimethylsiloxy) pyrrole (33) as the five-carbon homologative reagent. The synthesis of (1) and (2)is discussed in the context of retrosynthetic analysis. Carbaldehyde (25), has been prepared from both enantiomers of carvone, either (7) or (9), by application of a 15-step sequence with 4.7% and 5.4% overall yields respectively.

Stereoselective preparation of (5E)- and (5Z)-5-benzylidene-3-methyl-3-pyrrolin-2-ones. Application to the synthesis of ampullicine and isoampullicine

Abstract The application of N-Boc-5-phosphoranylidene- and N-Boc-5-diethylphosphonate-3-methyl-3-pyrrolin-2-ones to the stereoselective synthesis of (5E)- and (5Z)-3-methyl-5-benzylidene-3-pyrrolin-2-ones is examined. The stereoselective synthesis of the growth regulators Ampullicin and Isoampullicin by using both Wittig intermediates has also been achieved.

Decarbonylation of α-tertiary amino acids. Application to the synthesis of polyhydroxylated indolizidines

Abstract The decarbonylation of the bicyclic α-tertiary amino acid 16 easily obtained from D,L-pipecolic acid, is the key step in our strategy to prepare polyhydroxylated indolizidines. Thermal fragmentation of the acyl chloride 17 allowed us access to the enamide 19 , which has been described as a valuable intermediate in the synthesis of (±)-swainsonine.

Ti(III)-promoted radical cyclization of epoxy enones. Total synthesis of (+)-paeonisuffrone.

The total synthesis of (+)-paeonisuffrone starting from (+)-10-hydroxycarvone is described. The key step of our synthetic strategy is a titanium-catalyzed stereoselective cyclization initiated by epoxide opening through electron transfer. This reaction stereoselectively affords the highly oxygenated pinane skeleton present in the target molecule and opens a new and effective approach to the synthesis of the complex, biologically active terpenoids isolated from the roots of the Chinese paeony (Paeonia albiflora Pallas and Paeonia suffruticosa Andrews).

Stereoselective syntheses of syn 5-[1-hydroxy-2-(2-bromo-phenyl)-ethyl]-5-methyl-5H-furan-2-one and syn 5-[1-hydroxy-2-(2-methoxy-phenyl)-ethyl]-5-methyl-5H-furan-2-one

Abstract The aldol condensation of 2-(tert-butyldimethylsilyloxy)-5-methyl-furan 4 with several phenylacetaldehydes led stereoselectively to the syn or the anti aldols under fluoride- or Lewis-acid-promoted conditions. However low yields are obtained due to the formation of the double condensation products or aldols at C-3 site. An alternative six-step synthetic sequence was developed to access the target molecules starting from 2-bromo-phenyl acetaldehyde 20 and 2-methoxy-phenyl acetaldehyde 21. Structural assessment of the aldol products was achieved by stereospecific transformations and 1H NMR nOe experiments.

Synthetic studies towards (+)-Dihydroampullicin. Michael addition of N-Boc-2-(tert-butyldimethylsiloxy)-3-methyl-pyrrole to α-methylene lactones

Abstract The Michael addition of N -( tert -butoxycarbonyl)-2-( tert- butyldimethylsiloxy)-3-methyl-pyrrole ( 4 ) to several α-methylene lactones catalyzed by fluoride ions yielded the corresponding homologated products ( 26 – 30 ) with good yields. Application of this reaction to the sililoxy bicyclic lactone ( 5 ) allowed us to isolate the tricyclic lactone ( 26 ), a highly valuable intermediate in our synthetic strategy leading to the growth regulator (+)-Dihydroampullicin ( 1 ).