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Review
. 2023 Jul 13;21(7):402.
doi: 10.3390/md21070402.

Continuous Flow Chemistry: A Novel Technology for the Synthesis of Marine Drugs

Laura F Peña  1 , Paula González-Andrés  1 , Lucía G Parte  1 , Raúl Escribano  1 , Javier Guerra  1 , Asunción Barbero  1 , Enol López  1
Affiliations
Review

Continuous Flow Chemistry: A Novel Technology for the Synthesis of Marine Drugs

Laura F Peña et al. Mar Drugs. .

Abstract

In this perspective, we showcase the benefits of continuous flow chemistry and photochemistry and how these valuable tools have contributed to the synthesis of organic scaffolds from the marine environment. These technologies have not only facilitated previously described synthetic pathways, but also opened new opportunities in the preparation of novel organic molecules with remarkable pharmacological properties which can be used in drug discovery programs.

Keywords: drug discovery; flow chemistry; marine drugs; novel technologies; photochemistry.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Advantages of continuous flow chemistry.
Figure 2
Figure 2
Structure of aplysamine 6 (1).
Scheme 1
Scheme 1
First total synthesis of aplysamide 6 (1).
Scheme 2
Scheme 2
Continuous flow synthesis of aplysamine 6 (1).
Figure 3
Figure 3
Structure of (−)-hennoxazole A (15).
Scheme 3
Scheme 3
Retrosynthetic study of (−)-hennoxazole A (15).
Scheme 4
Scheme 4
Telescope synthetic protocol of fragment (5).
Scheme 5
Scheme 5
Assembly of the three fragments and final deprotection steps to obtain (−)-hennoxazole A (15).
Figure 4
Figure 4
Structure of vidarabine (31, AraA).
Scheme 6
Scheme 6
Schematic overview of the flow-biocatalyzed synthesis of vidarabine (31).
Scheme 7
Scheme 7
Biocatalyzed batch synthesis of vidarabine (31).
Scheme 8
Scheme 8
Chemical batch synthesis of vidarabine (31).
Figure 5
Figure 5
Structure of eribulin mesylate (37) or Halaven®.
Scheme 9
Scheme 9
Batch conditions used to obtain the derivative (41) in the synthesis of eribulin mesylate (37).
Scheme 10
Scheme 10
Flow reduction conditions of ester (38) with DIBAL-H.
Scheme 11
Scheme 11
Flow conditions of n-BuLi-mediated coupling reaction between sulfone intermediate (40) and aldehyde (39).
Scheme 12
Scheme 12
Retrosynthetic analysis of the C14-26 building block (42) of eribulin (37).
Scheme 13
Scheme 13
Enantioselective synthesis of alcohol (S)-45 in batch conditions under Cr(III)-catalytic propargylation.
Scheme 14
Scheme 14
Continuous-flow packed-bed reactor (PBR) used to obtain the enantiomeric pure alcohol (S)-45.
Figure 6
Figure 6
Structure of yessotoxin (50, YTX).
Scheme 15
Scheme 15
Conditions of reductive etherification used for building the H-ring of yessotoxin (50).
Scheme 16
Scheme 16
Scaled-up version of reductive etherification.
Scheme 17
Scheme 17
Reaction system under microfluidic conditions to afford the FGHIJ ring unit (52) of yessotoxin (50).
Figure 7
Figure 7
Structure of azaspiracids (57 and 58).
Figure 8
Figure 8
Representation of photobioreactiors in series for the production of AZA.
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References

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