78111-17-8 Usage
Uses
Used in Research:
Okadaic acid is used as a biochemical tool for studying cellular processes regulated by reversible phosphorylation of proteins, including control of glycogen metabolism, coordination of the cell cycle and gene expression, and maintenance of cytoskeletal structure.
Used in Tumor Promotion Studies:
Okadaic acid is used as a probe to deepen the knowledge of the mechanisms of cancer development in humans. It has been reported that other marine toxins, different from OA, can also act as specific protein phosphatase inhibitors and were proved to be able to cause skin, stomach, and liver tumors in animals. This has led some authors to suggest a new concept of tumor promotion: the okadaic acid pathway.
Note: Okadaic acid does not have any commercial applications in medicine, food, construction, or similar industries due to its toxicity and potential health risks.
Biological Activity
Potent inhibitor of protein phosphatase 1 (IC 50 = 3 nM) and protein phosphatase 2A (IC 50 = 0.2-1 nM). Displays > 100,000,000-fold selectivity over PP2B and PP2C. Tumor promotor. Shown to activate atypical protein kinase C in adipocytes.
Safety Profile
A poison by intraperitoneal route.Questionable carcinogen. Mutation data reported. Whenheated to decomposition it emits acrid smoke andirritating vapors
Toxicity evaluation
As the main representative DSP toxin, OA ingestion leads to the
onset of acute gastrointestinal symptoms typical of this intoxication (e.g., diarrhea, nausea, vomiting, abdominal pain). It
was suggested that diarrhea in humans is caused by hyperphosphorylation of ion channels in intestinal cells impairing
the water balance, or by increased phosphorylation of cytoskeletal or junctional elements that regulate solute permeability, resulting in passive loss of fluids. It was also suggested
that OA causes long-lasting contraction of smooth muscle from
human and animal arteries.At the molecular level, OA is a potent tumor promoter
and a recognized inhibitor of serine/threonine protein
phosphatases type 1 (PP1) and 2A (PP2A); PP2A is about
200 times more strongly inhibited than PP1. However,
nowadays OA is also known to inhibit PP4, and less effi-
ciently, PP5 and PP2B. This phosphatase activity inhibition
causes a dramatic increase in the phosphorylation levels of
numerous proteins that ultimately results in alterations of
relevant cell processes.Mostly because of this ability, OA was shown to induce
severe cytotoxic effects that include cell cycle alterations,
morphological changes, apoptosis, viability decreases, and
cytoskeleton disruptions on different cell systems. Besides,
genotoxicity after OA exposure was also reported (see Genotoxicity section), and it was also demonstrated to alter geneexpression patterns in OA-exposed cells. The existence of
OA-binding proteins other than phosphatases has been
demonstrated in several marine organisms but not in
humans.Although this toxin is not classified as a neurotoxin, it was
shown to induce some neurotoxic effects both in vitro and
in vivo. In vitro, OA induces apoptosis in a variety of human
and animal neurons, generates redistribution of neuronal
proteins, forces differentiated neuronal cells into the mitotic
cycle, induces disintegration of neuritis, and generates
changes in microtubule-associated proteins concomitant
with early changes in neuronal cytoskeleton. In vivo, OA
exposure was observed to produce inactivity and weakness in
mice as well as hyperexcitation, spatial memory deficit, and
neurodegeneration.
References
References/Citations:
Check Digit Verification of cas no
The CAS Registry Mumber 78111-17-8 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 7,8,1,1 and 1 respectively; the second part has 2 digits, 1 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 78111-17:
(7*7)+(6*8)+(5*1)+(4*1)+(3*1)+(2*1)+(1*7)=118
118 % 10 = 8
So 78111-17-8 is a valid CAS Registry Number.
78111-17-8Relevant articles and documents
Efficient synthesis of okadaic acid. 2. Synthesis of the C1-C14 domain and completion of the total synthesis
Sabes, Steven F.,Urbanek, Rebecca A.,Forsyth, Craig J.
, p. 2534 - 2542 (2007/10/03)
Described here are the full details of the preparation of a synthetic intermediate representing carbons 1' 14 (C1-C14) of the marine natural product okadaic acid (1), the coupling of this fragment with the previously prepared C15-C38 domain, and the completion of an efficient total synthesis of 1. The C1-C14 intermediate was prepared in 11 steps and ~20% overall yield from a functionalized δ-valerolactone derivative representing C3-C8 of 1. This featured a classic spiroketalization strategy to construct the highly substituted 1,7-dioxaspiro-[5.5]undec-4-ene system, followed by incorporation of the intact C1-C2 α-hydroxyl, α-methyl carboxylate moiety using cis-(S)- lactate pivalidene enolate. The complete C1-C14 intermediate was converted into 1 in five additional steps. Coupling of the C1-C14 fragment with the C15-C38 domain of 1 via C14 aldehyde and C15 β-keto phosphonate moieties provided the complete carbon skeleton of 1 bearing a ketone at C16 and a mixed-methyl acetal at C19. Reduction of the C16 ketone using Corey's (S)- CBS/BH3 system and subsequent acid-triggered spiroketalization formed the Central 1,6-dioxaspiro[4.5]decane ring system. Saponification of the C1-C2 pivalidene group and final reductive cleavage of the three benzyl ethers using lithium di-tert-butylbiphenylide in THF provided 1 in 48% yield from the C1-C14 aldehyde, and in 26 steps and ~2% overall yield in the longest linear sequence from the C22-C27 synthon methyl 3-O-benzyl-α-D- altropyranoside.
Total synthesis of the protein phosphatase inhibitor okadaic acid
Ley, Steven V.,Humphries, Alexander C.,Eick, Holger,Downham, Robert,Ross, Andrew R.,Boyce, Richard J.,Pavey, John B. J.,Pietruszka, Joerg
, p. 3907 - 3911 (2007/10/03)
The total synthesis of the protein phosphatase inhibitor okadaic acid 1 is reported using a convergent coupling strategy of three components, all of which may be prepared using chemistry developed in our laboratories.
Transformation of a Marine Toxic Polyether, Okadaic Acid
Ichikawa, Yoshiyasu,Isobe, Minoru,Goto, Toshio
, p. 975 - 982 (2007/10/02)
Natural okadaic acid 1 was transformed into the 7,24,27-tri-O-benzyl-1,2-acetonide derivative (4) in a 66 percent overall xield.The corresponding synthetic derivative (4) was identified with this authentic sample.
SYNTHESIS OF A MARINE POLYETHER TOXIN, OKADAIC ACID (4).TOTAL SYNTHESIS.
Isobe, Minoru,Ichikawa, Yoshiyasu,Bai, Dong-Lu,Masaki, Hisanori,Goto, Toshio
, p. 4767 - 4776 (2007/10/02)
Three segments A, B and C for okadaic acid synthesis were coupled with each other in order of A+(B+C), the key steps of the twice couplings being between sulfone carbanions and aldehydes.After the B+C coupling , the asymmetric center C-27 was generated by a hydride reduction of the corresponding ketone 16 under electronic control.The second coupling was followed to form the C-14/15 double bond.Oxidation of the α-oxy aldehyde 36 into the carboxylic acid group was achieved with sodium chlorite without C-1/C-2 bond cleavage.The total synthesis of okadaic acid was accomplished in 106 steps from commercially available D-glucose derivative s and butyne-diol.
SYNTHETIC STUDIES TOWARD MARINE TOXIC POLYETHERS THE TOTAL SYNTHESIS OF OKADAIC ACID
Isobe, Minoru,Ichikawa, Yoshiyasu,Goto, Toshio
, p. 963 - 966 (2007/10/02)
The total synthesis of okadaic acid has been accomplished through the coupling of all the segments, A, B and C, by means of sulfone-carbanion strategy.
