PMID- 38025058
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231201
IS  - 2296-2646 (Print)
IS  - 2296-2646 (Electronic)
IS  - 2296-2646 (Linking)
VI  - 11
DP  - 2023
TI  - Cleaner synthesis of preclinically validated vaccine adjuvants.
PG  - 1252996
LID - 10.3389/fchem.2023.1252996 [doi]
LID - 1252996
AB  - We developed synthetic glycophospholipids based on a glucosamine core (FP 
      compounds) with potent and selective activity in stimulating Toll-Like Receptor 4 
      (TLR4) as agonists. These compounds have activity and toxicity profiles similar 
      to the clinically approved adjuvant monophosphoryl lipid A (MPLA), included in 
      several vaccine formulations, and are now in the preclinical phase of development 
      as vaccine adjuvants in collaboration with Croda International PLC. FP compound 
      synthesis is shorter and less expensive than MPLA preparation but presents 
      challenges due to the use of toxic solvents and hazardous intermediates. In this 
      paper we describe the optimization of FP compound synthesis. The use of regio- 
      and chemoselective reactions allowed us to reduce the number of synthesis steps 
      and improve process scalability, overall yield, safety, and Process Mass 
      Intensity (PMI), thus paving the way to the industrial scale-up of the process.
CI  - Copyright (c) 2023 Romerio and Peri.
FAU - Romerio, Alessio
AU  - Romerio A
AD  - Department of Biotechnology and Biosciences, Universita degli Studi di 
      Milano-Bicocca, Milano, Italy.
FAU - Peri, Francesco
AU  - Peri F
AD  - Department of Biotechnology and Biosciences, Universita degli Studi di 
      Milano-Bicocca, Milano, Italy.
LA  - eng
PT  - Journal Article
DEP - 20231102
PL  - Switzerland
TA  - Front Chem
JT  - Frontiers in chemistry
JID - 101627988
PMC - PMC10651716
OTO - NOTNLM
OT  - TLR4
OT  - glycolipid
OT  - green chemistry
OT  - medicinal chemistry
OT  - optimization
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/11/29 18:42
MHDA- 2023/11/29 18:43
PMCR- 2023/01/01
CRDT- 2023/11/29 16:21
PHST- 2023/07/04 00:00 [received]
PHST- 2023/09/26 00:00 [accepted]
PHST- 2023/11/29 18:43 [medline]
PHST- 2023/11/29 18:42 [pubmed]
PHST- 2023/11/29 16:21 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 1252996 [pii]
AID - 10.3389/fchem.2023.1252996 [doi]
PST - epublish
SO  - Front Chem. 2023 Nov 2;11:1252996. doi: 10.3389/fchem.2023.1252996. eCollection 
      2023.