Download Introduction- Amino acid protection and deprotection is particularly

IntroductionAmino acid protection and deprotection is particularly common for making their
derivatives and it is very common for multistep synthesis
(1)
.Amino acid ester is an important
intermediate in organic synthesis there is variety of reagent for conversion of amino acid to
amino acid ester (2). Amino acid protection and deprotection is also used in peptide synthesis of
amino acid in solid and solution phase synthesis , the advantage of solution phase synthesis is to
isolate and characterized at every step(3)
An alpha-amino acid has the generic formula H2NCHRCOOH, where R is an organic
substituent; the amino group is attached to the carbon atom immediately adjacent to the
carboxylate group (the α–carbon). Other types of amino acid exist when the amino group is
attached to a different carbon atom; for example, in gamma-amino acids (such as gamma-aminobutyric acid) the carbon atom to which the amino group attaches is separated from the
carboxylate group by two other carbon atoms. The various alpha-amino acids differ in which
side-chain (R-group) is attached to their alpha carbon, and can vary in size from just one
hydrogen atom in glycine to a large heterocyclic group in tryptophan(4,6,19 ).
Protection and deprotection of amino acid have a vital role in synthesis of amino acid
derivative and peptide, deprotection of amino acid carried out using two condition i.e. acidic and
basic
conditions.
Most
commonly
used
for
protection
of
amino
group
are
tertiarybutylcarbonyl(Boc)/Trytyl(Trt)/3,5-Dimethoxyphenylisoproxycarbonyl(Ddz),2-(4Biphenyl)isoproxycarbonyl(Bpoc),2-nitrophenylsulfenyl(Nps) and these are deprotected by
acidic condition while group like
9-fluoenylmethoxycarbonyl(Fmoc)/2-(4-nitrophenylsulfonyl)ethoxycarbonyl(Nsc)/(1,1Dioxobenzo[b]thiophene-2
yl)methoxycarbonyl(Bsmoc),(1,1-Dioxonaptho[1,2-b]thiophene-2-
yl)methoxycarbonyl(α-Nsmoc)/1-(4,4-Dimethyl-2,6dioxocyclohex1-ylidene)-3methylbutyl(ivDde),2,7-Di-tert-butyl-Fmoc(Fmoc*) etc deprotected by basic condition in amino
acid(5,7) .
Amino acids are critical to life, and have many functions in metabolism. One particularly
important function is to serve as the building blocks of proteins, which are linear chains of amino
acids. Amino acids can be linked together in varying sequences to form a vast variety of proteins.
Twenty-two amino acids are naturally incorporated into polypeptides and are called
proteinogenic or standard amino acids. Of these, 20 are encoded by the universal genetic code.
Eight standard amino acids are called "essential" for humans because they cannot be created
from other compounds by the human body, and so must be taken in as food, It is also given in the
form of capsules,cachets,pills,granules,pellets,breads and particles(6,19,28,32).
Amino acid derivatives with prodrug like acyclovir (2-Amino-1, 9dihydro-9[(2-hydroxy
ethoxy) methyl] 6-H purin, 6-one) and ganciclovir produce valacyclovir and valgancyclovir
respectively are known to anti-viral drug. Amino acid ester with acyclovir gives valacyclovir
(Amino acid 2[2-amino-1, 6dihydro-6-oxo-9-H purin-9-yl] methoxy ethyl ester) that has greater
oral bioavailability (about 55%) than acyclovir (10–20%). Ester of L-valine with ganciclovir
gives valgancyclovir. After oral administration, it is rapidly converted to ganciclovir by intestinal
and hepatic esterase (7, 8, 9).
Fig-1
Valacyclovir (L-Valine 2[2-amino-1, 6dihydro-6-oxo-9-H purin-9-yl] methoxy ethyl
ester is an esterified version of acyclovir with Amino acid that has greater oral bioavailability
than acyclovir. It is converted by esterases to the active drug acyclovir, as well as the amino acid
valine, via hepatic first-pass metabolism. Acyclovir is
Fig-2
Acyclovir
Selectively converted into a monophosphate form by viral thymidine kinase, which is far
more effective (3000 times) in phosphorylation than cellular thymidine kinase. Subsequently, the
monophosphate form is further phosphorylated into the active triphosphate form, aciclo-GTP, by
cellular kinases. Aciclo-GTP is a very potent inhibitor of viral DNA polymerase; it has
approximately 100 times higher affinity to viral than cellular polymerase. Its monophosphate
form also incorporates into the viral DNA, resulting in chain termination. It has also been shown
that the viral enzymes cannot remove aciclo-GMP from the chain, which results in inhibition of
further activity of DNA polymerase. Aciclo-GTP is fairly rapidly metabolised within the cell,
possibly by cellular phosphatases (8, 9).
Fig-3 Valacyclovir Hydrochloride
Oral bioavailability is approximately 60%. Fatty foods significantly increase the
bioavailability and the peak level in the serum. It takes about 2 hours to reach maximum
concentrations in the serum.Valganciclovir is eliminated as ganciclovir in the urine, with a halflife of about 4 hours in people with normal kidney function. The mechanism of this drug is
activation via thymidine kinase enzyme. The phosphotransferase enzyme can likewise activate
valgancyclovir (10, 11, 12).
Fig-4 Valgancyclovir Hydrochloride
Preparation of these drugs using some new method is also important tool in
synthesis of prodrug .It also help to reduce commercial value of these drugs. For this use of
cheep reagent, protecting group is useful to get product of good quality and yield of product.
These all above mentioned product have great demand in medicinal field (7, 8, 14)