Trisporic acid

The phosphonate (176) has been used for the addition to aldehydes of a masked jS-keto-ester function and applied in the synthesis of ( )-7(f),9(t)-trisporic acid B methyl ester. The isomerically pure phosphonate (177) has been used in a synthesis of dehydro-Cig juvenile hormone," the anion being generated by treatment with lithium di-isopro-pylamide in THF-HMPT at - 65 °C for 1 min. 

Other Degraded Carotenoids. A new synthesis of the fungal sex hormone ( )-(7 , 9 )-trisporic acid B methyl ester (114) utilized as the key step a Michael-aldol sequence on the /3-keto-ester (115) to yield the highly functionalized cyclo-hexenone (116). The latter underwent Wittig reaction with the phosphonium salt (117) to give (114). After basic alumina-catalysed hydrogen exchange in tritiated... 

The mating-type-specific prohormones of Blakeslea trispora (Mucorales), precursors of trisporic acid (27), have been investigated.19 The minus strain produces four prohormones (28)—(31), all previously characterized compounds,20 whereas the plus strain produces one prohormone which was characterized as (32). The stereochemistry at C-4 was assigned tentatively from consideration of m.s. data. 

The compound (121), a useful intermediate in trisporic acid (27) synthesis has been prepared 55 from Hagemann s ester (123). An alkylation sequence in which first a methyl group and then a methallyl group were introduced into (123) gave the... 

Addition of vitamin A to a medium supporting the growth of Phycomyces blakesleeanus led to a large increase in the j8-carotene content of the wild strain,362 although the additive was not itself converted into product. Vitamin A is possibly sufficiently similar in structure to the natural regulators of carotenogenesis (possibly trisporic acids) as to be able to simulate their effect. 

Two syntheses of trisporic acid B methyl ester (52) have been reported (Scheme 4). Both groups reversed the previous assignment of stereochemistry about the 9,10-double bond. 

A bicyclic y-lactol—accessible in a few steps— allows entry into certain vinylcyclopro-panes (equation 117). At high temperature, these suffer a hydrogen shift to 1,4-dienes, which are masked 1,4-dicarbonyl compounds capable of many synthetically valuable selective reactions ". A total synthesis of trisporic acids profits from this approach ". If simple Grignard reagents are added to the y-lactol, manipulation of the resulting cyclopropylcarbinols opens a path to 2-methylenecyclobutanones. ... 

Details have appeared of the use of the ylide Bu8P CHCO(CH2)4CHj in prostaglandin synthesis and of the synthesis of ectocarpen and related cycloheptadienes. Among other syntheses involving the use of ylides in key steps are those of acyclic analogues of trisporic acids, urushiol, a sesqui-... 

A number of terpenoids appear to be derived from carotenoids by cleavage of the polyene chain. These include retinal (C20). trisporic acids (Cig), abscisic acid (C15), a-ionone (C13), and loliolide (Cu). 

The fungal hormones trisporic acids B and C were shown to have a carotenoid origin. The absolute stereochemistry of trisporic acid C (82) was established by ozonolysis and c.d. measurements. In addition to the all-trons isomers, 9-cis trisporic acids are also present." ... 

Two analogues (141) and (142) of trisporic acid (143) have been synthesized in high overall yield ... 

Molecules like bisabolene with several alternative first disconnections are typical cases where it is helpful to consider convergence. The fungal metabolite trisporic acid (15) is a more testing example. The two central double bonds (a) and (b) offer possible Wittig disconnections. The less central (b) leads to an easily synthesised halide (17) (Chapter 25) and a difficult ketone (16), but the more central (a) leads to two nearly equal fragments (18) and (19) and to a more convergent synthesis. 

The Robinson annelation goes in one step in base and acid hydrolysis releases aldehyde (27) which gives trisporic acid after the convergent Wittig reaction and hydrolysis. The double bond is E as the ylid from (19) is conjugated (Chapter 15). 

The stereochemistry of the cyclization of lycopene has been discussed by Britton. He concluded that, based on the absolute stereochemistry of trisporic acid and a-carotene, the cyclization involves the initial formation of a boat conformer. However, this deduction assumes that both the a- and j5-ring systems are formed from the same carbonium ion . 

TRISPORIC ACID AND THE CONTROL OP SEXUAL DIFFERENTIATION IN THE MUCCXIALES... 

Trisporic acid is the sex hormone of the fungi of the order Mucorales, It is not produced by unmated cells of the two mating types, but when (+) and (-) cells are close enough so that metabolites can diffuse between them they initiate a collaborative biosynthesis of trisporic acid, which diffuses into the medium. It affects the differentiation and isoprenoid biosynthesis of recipient cells. 

Trisporic acids (Fig. 1) are compounds with a profound physiological action. They are produced by, and act solely on, fungi of the order Mucorales where they control sexual differentiation. The majority of species are heterothallic, where conjugation occurs between two different but compatible... 

The mechanism of p—carotene cleavage is still unproven, but probably involves oxidative 15,15 cleavage to retinal. The sequence involves the loss of a C2 unit, a reduction of the 11,11 double bond and a series of oxidations. The nature of the proposed metabolic grid, with the different steps in the two different mating types, explains why trisporic acid is only synthesised when the two thalli are in diffusion contact i.e. the intermediates (and/or enzymes) can then diffuse from one cell to the other to complete the metabolic pathway. 

We have preliminary evidence that in (-) M mucedo trisporic acid is taken up more rapidly in the ionised form In the period 0 25-10 min after the addition of trisporic acid to (-) M mucedo in phosphate buffer pH 5.0 there was a 97% relative fall in the hormone level in the medium as measured by u.v spectroscopy The kinetics of the uptake were approximately logarithmic In a parallel experiment with trisporic acid in the un-ionised form at pH 4.0, uptake by ( ) M. mucedo was slower with non-logarithmic kinetics It took 20 min to achieve a 97% relative reduction in medium hormone levels and there was evidence of a short lag phase (Fig 4). 

Once through the wall, the cell membrane represents another barrier where the same criteria for passage apply Considering the structure of trisporic acid it might be expected easily to become incorporated into the membrane but less likely to cross it by a passive mechanism ... 

All these considerations of trisporic acid transport into the cell also apply to the prohormones These compounds may need to be transported across the cell membrane for it is probably... 

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